Tuesday, December 9, 2008

Growth Hormone in Shwachman-Diamond Syndrome

I cut and pasted from the eMedicine article. Such a shame that medical professionals still cannot SPELL the disease. SIGH.

Growth hormone has been used to treat children with Schwachman-Diamond syndrome who have growth hormone deficiency. The initial response is good; however, long-term therapy with growth hormone is unsuccessful.

It comes from the eMedicine article on SDS found here: http://www.emedicine.com/ped/topic2060.htm

The reference is gives is: Marseglia GL, Bozzola M, Marchi A, et al. Response to long-term hGH therapy in two children with Schwachman- Diamond syndrome associated with GH deficiency. Horm Res. 1998;50(1):42-5

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Shwachman-Diamond Syndrome Registry

You can contact the SDS registry for info on how to register. Melissa Alvendia malvendi@fhcrc.org Questionnaires are available, but the website is not up and running yet. It will hopefully be on-line soon. They also have pamphlets in PDF…but the margins are off when they are printed. They are working on getting all the supporting organizations a flyer that is easier to print. I just got an email about the flyer last night—so hopefully it will be soon.

The website for the registry will be located at www.SDSRegistry.org

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Monday, December 8, 2008

SBDS-deficiency results in specific hypersensitivity to Fas stimulation and accumulation of Fas at the plasma membrane.

Apoptosis. 2008 Nov 14.

SBDS-deficiency results in specific hypersensitivity to Fas stimulation and accumulation of Fas at the plasma membrane.
Watanabe KI, Ambekar C, Wang H, Ciccolini A, Schimmer AD, Dror Y.

Shwachman-Diamond syndrome (SDS) is an inherited disorder characterized by reduced cellularity in the bone marrow and exocrine pancreas. Most patients have mutations in the SBDS gene, whose functions are unknown. We previously showed that cells deficient in the SBDS protein are characterized by accelerated apoptosis and Fas hypersensitivity, suggesting that the protein might play an important role in Fas-mediated apoptosis. To study the mechanism of Fas hypersensitivity, we compared shRNA-mediated SBDS-knockdown HeLa cells and SDS marrow CD34+ cells for their sensitivity to several groups of apoptosis inducers. Marked hypersensitivity was noticed in response to Fas stimulation, but not to tumor necrosis factor-alpha, DNA-damaging agents, transcription inhibition or protein synthesis inhibition. To identify the Fas signaling factors that cause hypersensitivity, we analyzed the expression of the pathway's proteins. We found that Fas accumulated at the plasma membrane in SBDS-knockdown cells with corresponding expression of Fas transcript 1, the main Fas transcript which contains both the transmembrane domain and the death domain. However, the total levels of Fas protein and mRNA were comparable to controls, and Fas internalization occurred normally. Expression of FADD, caspase-8 and -3 were not elevated and the pathway inhibitors: ERK, c-FLIP and XIAP were not decreased. These results suggest that SBDS loss results in abnormal accumulation of Fas at the plasma membrane, where it sensitizes the cells to stimulation by Fas ligand.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A.

I have the full-text of this one-- very interesting article!

Blood Cells Mol Dis. 2008 Nov 15.

Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A.
Nihrane A, Sezgin G, Dsilva S, Dellorusso P, Yamamoto K, Ellis SR, Liu JM.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and leukemia predisposition, pancreatic exocrine dysfunction, and skeletal abnormalities, manifesting as skeletal dysplasia and osteoporosis. Mutations in SBDS have been shown to cause SDS, but the function of the SBDS gene product is unclear. Accelerated angiogenesis has recently been described in bone marrow cells from SDS patients. To clarify the unknown function of SBDS, we performed experiments analyzing the cellular effects of depleting SBDS by RNA interference. The growth of HeLa cells constitutively depleted of SBDS was markedly hindered when compared to cells stably transfected with siRNA against an irrelevant control gene. Similarly, growth of HeLa cells induced to express siRNA against SBDS was specifically inhibited. Inducible SBDS knockdown was associated with modestly increased levels of apoptosis, suggesting a partial contribution of this process to growth inhibition. By microarray analysis of knockdown cells, we found marked differences in expression of genes in multiple pathways, and we chose to examine a selected subset more closely using quantitative PCR arrays. In constitutive and inducible SBDS-depleted HeLa cell clones, we found 3- to 6-fold elevated mRNA levels of osteoprotegerin (OPG or TNFRSF11B) and vascular endothelial growth factor-A (VEGF-A). We confirmed significant overexpression of both secreted proteins by ELISA from supernatants of SBDS-depleted HeLa cells. Osteoprotegerin and VEGF-A are known to have diverse effects on osteoclast differentiation, angiogenesis, and monocyte/macrophage migration, all processes that may be aberrant in SDS, and we propose that overexpression of these factors may contribute to its pathology.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Totipotent stem cells bearing del(20q) maintain multipotential differentiation in Shwachman Diamond syndrome.

Br J Haematol. 2008 Nov 11.
Totipotent stem cells bearing del(20q) maintain multipotential differentiation in Shwachman Diamond syndrome.

Crescenzi B, La Starza R, Sambani C, Parcharidou A, Pierini V, Nofrini V, Brandimarte L, Matteucci C, Aversa F, Martelli MF, Mecucci C.

Summary SBDS/7q11 gene mutations underlie the congenital Shwachman Diamond syndrome (SDS), characterized by bone marrow failure and high risk of haematological malignancies. In two cases of SDS with bone marrow failure and isolated del(20q) interphase fluorescence in situ hybridization (I-FISH) found no abnormalities in FHIT/3p14.2, IKZF1/7p13, D7S486/7q31, PTEN/10q23.3, WT1/11p13, ATM/11q23, D13S25/13q14, TP53/17p13, NF1/17q11, SMAD2/18q21, RUNX1/21q22. Fluorescence immunophenotype combined with I-FISH found del(20q) in a totipotent haematopoietic stem cell (CD34(+), CD133(+)) and downstream myelocyte (CD33(+), CD14(+), CD13(+)), erythrocyte (Glycophorin A(+)) and lymphocyte lineages (CD19(+), CD20(+), CD3(+), CD7(+)). These findings and clinical follow-ups confirm the benign course of SDS with isolated del(20q).

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Monday, November 24, 2008

Fecal fat

here are a few good links for information on fecal fat tests and results:


This site has pediatric reference ranges:


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Sunday, November 2, 2008

Shwachman-Diamond Syndrome Information

This site has information on SDS including the common cytogenetic findings in SDS, telomeres, and information on P53 protein overexpression. http://atlasgeneticsoncology.org/Kprones/ShwachmanID10058.html

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Thursday, October 2, 2008


Thank you to all who made this video possible-- the camera crews, the doctors who spoke and Jules who jumped out of the airplane! Great awareness video!

Iron Deficiency Anemia - Iron Stores

Great site about Iron Deficiency Anemia. Also has info on iron stores in the marrow along with pictures.


Shwachman-Diamond Syndrome on Mystery Diagnosis

Part one:

Part two:

Friday, September 19, 2008

Bone Scans

Here are a few articles that will be helpful in understanding bone scans:



Bone scans detect inflammation, cancer and new bone growth......

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Wednesday, September 17, 2008

Iron Testing

DrGreene Content

The "Iron Test" FailsMany children in the United States get a simple screening blood test to check for iron deficiency – but the test doesn't work! The test does identify anemia (not enough red blood cells) by measuring either the hemoglobin level (hgb) or the hematocrit (hct). But parents are often told that if the test is low, the child needs more iron – or that if the test is normal, the child's iron level is fine. Because getting enough iron is so important to normal development, the screening test is required by many Medicaid insurance programs. All children must have the test to qualify to get food in the Supplemental Nutrition Program for Women, Infants, and Children. But the test had not been checked for accuracy in the last twenty years. According to a study in the February 2005 Pediatrics, the test fails to identify most kids with iron deficiency. It's true that kids with iron deficiency are more likely to be anemic than other kids, but the correlation is not strong enough to make the test useful. The test is wrong more often than it is right. More than two thirds of the children with a low hgb or hct have normal iron levels. They are anemic for other reasons, such as a recent viral illness or genetic trait. More disturbingly, more than two thirds of the children who are truly iron deficient will have a normal screening test. We routinely fail to identify children whose iron levels are low enough to affect their intelligence. We need better tests. In the meantime, it's important to be sure that toddlers have diets that are rich in iron or take a multivitamin with iron.
Alan Greene MD FAAPOrginally published: February 25, 2005

from this link: http://www.drgreene.com/21_1881.html

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Sunday, September 14, 2008

p53 Protein

p53 protein overexpression in Shwachman-Diamond syndrome / In reply
Archives of Pathology & Laboratory Medicine, Oct 2002 by Dror, Yigal, Elghetany, M Tarek, Alter, Blanche P

To the Editor.-We read with great interest the paper of Drs Elghetany and Alter in the April 2002 issue of the ARCHIVES.1 Shwachman-Diamond syndrome (SDS) is an autosomal recessive multisystemic disorder characterized by varying degrees of marrow failure and a high propensity for malignant myeloid transformation into myelodysplastic syndromes (MDS) and acute myeloid leukemia.2-4 The authors found p53 overexpression in bone marrow biopsies from 9 patients with SDS. None of the bone marrow biopsies from patients with acquired aplastic anemia or acquired cytopenias and none of those from individuals in the control group had overexpression of p53 protein. Very interestingly, p53 overexpression in patients with SDS was comparable to p53 results in 46 bone marrow specimens from patients with refractory anemia. Refractory anemia is a subtype of MDS.
Although neither the method for selecting patients nor the clinical phenotype of the patients was specified in the paper, the authors' work is important and furthers our understanding of the relationship between SDS and MDS. Myelodysplastic syndrome is a preleukemic, stem cell disease with peripheral blood cytopenia, ineffective hematopoiesis, and varying degrees of bone marrow cellularity and dysplasia. Shwachman-Diamond syndrome meets many of these criteria2: it is a stem cell disorder with peripheral cytopenia, ineffective hematopoiesis,5,6 and varying degrees of bone marrow cellularity, and it carries a significantly increased risk of leukemia.2-4 In addition, scattered mild dysplastic changes in the erythroid, myeloid, and megakaryocytic precursors are commonly seen on careful examination of bone marrow biopsies of patients with SDS2 and are part of the syndrome. Further, the close relationship between SDS and MDS is reflected by similar defects in marrow stromal support of normal hematopoiesis,5 increased apoptosis mediated through the Fas pathway,6 a high frequency of clonal marrow cytogenetic abnormalities,2 and as the authors showed also by a prevalence of p53 protein overexpression that is similar to that in patients with refractory anemia.1 Therefore, SDS seems to be a myelodysplastic disorder from its inception. We therefore consider SDS to be refractory anemia 2 or refractory cytopenia according to the CCC (category-cytology-- cytogenetics) classification of childhood MDS.7 When we refer to malignant myeloid transformation in SDS, we mean stages beyond refractory anemia, namely refractory cytopenia with cytogenetic abnormality, refractory anemia with ring sideroblasts, refractory anemia with dysplasia, refractory cytopenia with excess blasts, or leukemia.
We have recently analyzed bone marrow mononuclear cells from 11 patients with SDS (2 had a clonal marrow cytogenetic abnormality), and we did not find mutations in exons 2 through 11 of the p53 gene.2 Therefore, p53 protein overexpression in SDS can result from either upregulation of the functional p53 gene (as the authors postulated) or posttranslational modification of the protein, rendering it more stable than the wild type protein, which normally cannot be detected.
Marrow Failure and Myelodysplasia Programme
Division of Hematology/ Oncology
The Hospital for Sick Children and the University of Toronto
Toronto, Ontario, Canada M5G 1X8
1. Elghetany MT, Alter BP. p53 Protein overexpression in bone marrow biopsies of patients with Shwachman-Diamond syndrome has a prevalence similar to that of patients with refractory anemia. Arch Pathol Lab Med. 2002;126:452-455.
2. Dror Y, Durie P, Ginzberg H, et al. Clonal evolution in marrows of patients with Shwachman-Diamond syndrome: a prospective 5-year follow-up study. Exp Hematol. 2002;30:659-669.
3. Mack DR, Forstner GG, Wilschanik M, Freedman MH, Durie PR. Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression. Gastroenterology. 1996;111:15931602.
4. Smith OP, Hann IM, Chessells JM, Reeves BR, Milla P. Haematological abnormalities in Shwachman-Diamond syndrome. Br] Haematol. 1996;94: 279-284.
5. Dror Y, Freedman MH. Shwachman-Diamond syndrome: an inherited preleukemic bone marrow failure disorder with aberrant hematopoietic progenitors and faulty marrow microenvironment. Blood 1999;94:3048-3054.
6. Dror Y, Freedman MH. Shwachman-Diamond syndrome marrow cells show abnormally increased apoptosis mediated through the Fas pathway. Blood. 2001;97:3011-3016.
7. Mandel K, Dror Y, Poon A, Freedman MH. Practical classification of pediatric MDS. J Pediatr Hematol Oncol. 2002;24:343-352.
In Reply.-We thank Dr Dror for his comments in support of our recent article.1 Our patients were unselected, and included all of those whose samples were available between November 1999 and November 2000. None of the patients with Shwachman-Diamond syndrome (SDS) had cytogenetic clones, and their bone marrow morphology did not show significant dysplastic features. Thus, p53 overexpression was the hallmark of the similarity between SDS and refractory anemia (RA). Dr Dror raises the interesting question regarding the relationship between this syndrome and RA. Although we agree with Dr Dror that SDS shares common features with RA, it may not be appropriate to classify all patients with this syndrome as having RA at the time of diagnosis. Other bone marrow failure syndromes, such as Fanconi anemia and Diamond-Blackfan anemia, share some features with RA as well.2,3 We are concerned that labeling SDS as RA may prompt an aggressive mode of treatment that may not be supported by data other than these similarities. Moreover, there are some indications that myelodysplastic syndromes evolving from an inherited bone marrow disease may not have the same biological behavior as primary myelodysplastic syndromes in children.4 Longterm prospective studies and the continued search for an underlying molecular defect for SDS should shed some light on this rare disease and its relationship to RA.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Medications that Cause Neutropenia

Here is a link to a site that lists medications that can cause neutropenia:


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Thursday, September 11, 2008

Types of Eczema

Types of Eczema (Dermatitis)
Allergic contact eczema (dermatitis): a red, itchy, weepy reaction where the skin has come into contact with a substance that the immune system recognizes as foreign, such as poison ivy or certain preservatives in creams and lotions

Atopic dermatitis: a chronic skin disease characterized by itchy, inflamed skin

Contact eczema: a localized reaction that includes redness, itching, and burning where the skin has come into contact with an allergen (an allergy-causing substance) or with an irritant such as an acid, a cleaning agent, or other chemical

Dyshidrotic eczema: irritation of the skin on the palms of hands and soles of the feet characterized by clear, deep blisters that itch and burn

Neurodermatitis: scaly patches of the skin on the head, lower legs, wrists, or forearms caused by a localized itch (such as an insect bite) that become intensely irritated when scratched

Nummular eczema: coin-shaped patches of irritated skin-most common on the arms, back, buttocks, and lower legs-that may be crusted, scaling, and extremely itchy

Seborrheic eczema: yellowish, oily, scaly patches of skin on the scalp, face, and occasionally other parts of the body

Stasis dermatitis: a skin irritation on the lower legs, generally related to circulatory problems

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Eczema - atopic dermatitis

Merck Atopic Dermatitis Article

Great info and pictures with this article. Includes causes and treatment.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Merck Neutropenia Article

Merck Neutropenia Article

Great article on Neutropenia, causes and degrees. Talks about inflammation of response (when ANC is below 200, inflammation response can be gone). Very detailed!

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Wednesday, September 10, 2008

Mitochondriopathie bei einem Kind mit Shwachman-Syndrom und Zöliakie Fallbericht = Rare combination of celiac disease and respiratory-chain-defect wit

Mitochondriopathie bei einem Kind mit Shwachman-Syndrom und Zöliakie Fallbericht = Rare combination of celiac disease and respiratory-chain-defect with Shwachman syndrome. Case report
Auteur(s) / Author(s)
CASTRO FRENZEL B. (1) ; DAS A. M. (2) ; MARG W. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Prof.-Hess-Kinderklinik, Zentrum für Kinderheilkunde und Jugendmedizin, Zentralkrankenhaus Sankt-Jürgen-Strasse, Bremen, ALLEMAGNE
(2) Universitäts-Kinderklinik Hamburg-Eppendorf, ALLEMAGNE

Résumé / Abstract
Background. The Shwachman syndrome represents one of the causes of exocrine pancreatic insufficiency, surpassed in incidence only by cystic fibrosis. It is a heriditary multi-organ disease with effects on pancreatic function, hematopoesis and growth of cartilage and bone. Case report. In our case, who presented with a rare combination of celiac disease and diabetes mellitus, we want to emphasise the large variability of clinical signs and symptoms.The pathogenesis of Shwachman syndrome is not delineated.The case presented here showed a respiratory-chain-defect in complex II, IV and V in fibroblast culture. Conclusions. We propose patients with Shwachman syndrome to investigate for respiratory-chain defect.This could help for better classification and diagnosis of this syndrome.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Thursday, September 4, 2008

Anemia of Chronic Disease as a Harmful Disease State or Beneficial Adaptation

This comes from the National Anemia Action Council: http://www.anemia.org/professionals/reviews/content.php?contentid=000234&sectionid=00014

Anemia of Chronic Disease as a Harmful Disease State or Beneficial Adaptation
NAAC Review Published: September 4, 2008
It is commonly believed that anemia of chronic disease (ACD) is an adverse consequence of systemic illness and should be treated. In this analysis, Zarychanski and Houston propose that ACD is not an adverse consequence, but a beneficial adaptive response to an underlying disease state. They present three arguments in support of this hypothesis.
First, the observation that anemia is associated with a poor prognosis is not evidence of causation. Although several studies identify anemia as an independent predictor of poor prognosis, this association cannot be considered as causation. In fact, the opposite may be true; both the degree of anemia and the prognosis may simply reflect the severity of the underlying disease. Since routinely measured clinical variables do not reliably measure inflammatory and stress responses, it is difficult to adjust for these effects. Several studies in heart disease and cancer, not specifically designed to study ACD, showed that anemia was not an independent predictor of survival when the studies were adjusted for these variables and other clinical factors.
Second, anemia of chronic disease has the characteristic of an adaptive physiologic response. ACD appears to be a highly coordinated response to systemic disease. The occurrence of several independent processes contributing to hemoglobin reduction, suggests a process of evolutionary adaptation. Iron sequestration is the best studied, and its potential beneficial effects include inhibition of bacterial growth and attenuated production of reactive oxygen species. Also, decreased bone marrow production reduces nutrient utilization in times of stress. Moderate anemia and compensatory expansion of plasma volume reduces blood viscosity, which decreases left ventricular stroke and may improve microvascular perfusion. Lastly, decreased margination of platelets and decreased scavenging of nitric oxide may also reduce thrombosis.
Third, treatment of mild to moderate anemia appears to increase mortality. If ACD is a protective measure, efforts to override this mechanism by increasing hemoglobin should elicit adverse consequences. This is seen in several studies − not specifically designed to study ACD − that have evaluated red blood cell transfusions or the use of erythropoietin stimulating agents. Among critically ill patients, patients with acute coronary syndrome or myocardial infarction, several observational studies showed transfusions to be an independent risk factor for mortality. Two recent meta-analyses of renal failure patients and cancer patients showed that treatment with erythropoietin to achieve a “normal” hemoglobin was associated with higher mortality compared to regimens designed to achieve lower target hemoglobin levels.Even if ACD is a beneficial adaptive response, this response may sometimes be excessive or insufficient, and therefore maladaptive and potentially harmful. Nevertheless, the authors believe there is sufficient evidence to advocate restraint regarding the treatment of mild to moderate ACD. The possible risks of treatment should be weighed carefully against the potential benefits before therapy to override ACD is considered.
Zarychanski R, Houston DS. Anemia of chronic disease: a harmful disorder or an adaptive, beneficial response? CMAJ. 2008 Aug 12;179(4):333-7.
NAAC Expert Commentary: In their provocative article, Zarychanski and Houston address the old age question asked by many in the medical field for years; is anemia a disease state or an adaptation? The authors postulate that anemia of chronic disease (ACD) is an adaptive response to an underlying condition that confers benefit to the patient and treatment is essentially harmful. There are many other medical conditions when pathologic states are a result of adaptation. For example, cardiomagaly in congestive heart failure, carbon dioxide retention in obstructive pulmonary disease, etc.
According to the authors, anemia may represent a special case since it is usually associated with another underlying disease or is a signal of one. Although scores of many more publication not presented here relate anemia to poor prognosis, they all rely on association and not direct causation, as pointed out by the authors. The lack of causation data does not negate the fact that anemia may still be a marker of poor prognosis and survival. In their argument they mix data derived from acute anemia (blood loss) with data (mostly meta-analysis) from studies done in chronic conditions. Although many patients seem to tolerate mild to moderate anemia, it is yet to be concluded that their quality of life (including exercise tolerance) would not improve with treatment.
Treatment of mild to moderate anemia with blood transfusion is counter-productive as stated by the authors. It is short term, requires an invasive procedure and is also associated with short and long term negative outcomes. In contrast, the use of erythropoietin (EPO) has been shown to improve both the quality of life and performance of patients suffering from renal failure and cancer. In three randomized controlled studies performed in critically ill patients, EPO raised hemoglobin, reduced exposure to transfusions in two studies and had a positive survival outcome in the last of this series. Deep vein thrombosis (DVT) has been established as risk in these patients and DVT prophylaxis is now recommended, although already the standard of care.
Dosing and hemoglobin targets have surfaced as the suspected reasons for poor outcome in both renal failure and cancer patients with or without chemotherapy treatments. To suggest that ‘treatment’ is harmful may deprive many of a better quality of life while sparing the few who suffer untoward complications.
In summary, this study contends that anemia is beneficial and an adaptive response to illness, rather than a disease state. The authors conclude that while evidence does support their hypothesis, further clinical trials are necessary to illuminate the mechanisms of these interactions. We agree more studies are needed to validate these theories, and we also encourage further exploration of the argument for anemia as a disease state. However, evidence is lacking for the authors to regard treatment of mild to moderate ACD as harmful, and some evidence also shows that treatment may in fact be beneficial. In either case, thought and care should be taken prior to instituting therapy for ACD, something the authors endorsed and a notion which should be applied to any medical therapeutic intervention.
View original published article at PubMed

Additional Materials in...
More Research Reviews in: Clinical Practice, HematologyFeature Articles: Clinical Practice, HematologyAsk The Expert: Clinical Practice, Hematology

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Wednesday, September 3, 2008

Shwachman Diamond syndrome-phenotypes and genotypes: when clinical research informs biology.

I read the full-text comment and it was another interesting piece.

Shwachman Diamond syndrome-phenotypes and genotypes: when clinical research informs biology.

Pediatr Blood Cancer. 2008 Oct;51(4):449-50.

Comment on:
Pediatr Blood Cancer. 2008 Oct;51(4):461-7.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Shwachman-Diamond syndrome in a child presenting with cystic fibrosis-type symptoms and a false-positive sweat test.

I just read the full-text of this article:

Shwachman-Diamond syndrome in a child presenting with cystic fibrosis-type symptoms and a false-positive sweat test.
J R Soc Med. 2008 Jul;101 Suppl 1:39-43

Very interesteing. No abstract is available.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Help Books

Books to help kids
Our youngest has a workbook to help him with his worries. We found others by the same author. We ordered one of them, but I wanted to post them all -- it might help someone.
What to Do When Your Temper Flares: A Kid's Guide to Overcoming Problems with Anger by Dawn Huebner, Bonnie Matthews (Illustrator)(Paperback)
What to Do When You Grumble Too Much: A Kid's Guide to Overcoming Negativity(Paperback)
What to Do When you Dread Your Bed: A Kid's Guide to Overcoming Problems with SleepBoy and a Bear: The Children's Relaxation Book
What to Do When Your Brain Gets Stuck: A Kid's Guide to Overcoming Ocd by Dawn Huebner, Bonnie Matthews (Illustrator)

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Wednesday, August 20, 2008

CBC Information

WebMD explains parts of a complete blood count

This is a very informative article that explains each portion of the CBC in detail.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Friday, August 8, 2008

Blood and Blood Cells

An informative site about blood production and various items found on a complete blood count with differential.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Thursday, August 7, 2008

Tuesday, August 5, 2008

Pediatric Reference Ranges

Pediatric Reference Ranges

Great charts with normal CBC and differential ranges as well as a few others.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Saturday, August 2, 2008

Mlabsorption article-Fecal Fat norm/ Steatorrhea defined

Malabsorption Article from Specialty Labs

Print View
E. Robert Wassman, M.D.& Hermino R. Reyes, Ph.D.

A wide variety of disease states cause malabsorption as a primary or secondary feature. Malabsorption can be pancreatic, hepatic, or enteric in origin, and can be generalized or specific in nature. In general malabsorption, steatorrhea, defined as >5 g of fat in feces per 24 hours, is a major sign.1 The development of age-specific reference values for the fecal acid steatocrit permits the distinction of "physiological steatorrhea" during the first six months of life.2

In malabsorption of pancreatic origin, digestion and subsequent small bowel absorption is impaired. Creatorrhea, the presence of undigested meat fibers in the stool, can also be present. Pancreatic malabsorption is seen with pancreatitis, cancer of the pancreas, and cystic fibrosis (CF). CF can be differentiated by the measurement of sweat electrolytes, stool trypsin,1 or more recently, a specific DNA test for gene mutations.

Hepatic malabsorption, usually accompanied by other signs of liver disease, results from decreased availability of bile salts necessary for fat emulsification. It can occur in combination with pancreatic malabsorption when tumors obstruct drainage from both organs.1 Elevated plasma lathosterol measured by gas liquid chromatography has a 100% sensitivity and 82% specificity for bile acid malabsorption, and is simpler and less expensive than fecal bile acid determination, the 75SeHCAT test or the Schilling test.3

Enteric malabsorption occurs in a wide variety of conditions with normal digestion but reduced assimilation including blind loop syndrome (bacterial overgrowth), diverticulosis of the small intestines, Whipple disease, lymphoma, amyloidosis, shortened bowel length, celiac disease and other food sensitivities, radiation therapy, vasculitis, diabetes, carcinoid, hypogammaglobulinemia and other immunodeficiencies. Most have unique laboratory findings in addition to malabsorption. Enteric malabsorption can be distinguished from the pancreatic forms by the D-xylose absorption test which measures the urinary excretion of the sugar over five hours after ingestion of a 25 gram oral dose. Because pancreatic enzymes play no role in its absorption, the excretion of <3 g in this period is indicative of an enteric malabsorption; in the face of concomitant renal disease, serum concentrations should be simultaneously evaluated. Clinical associations of celiac disease (CD) can include mild weakness, bone pain, aphthous stomatitis, chronic diarrhea, abdominal bloating, progressive weight loss, dermatitis herpetiformis (DH), hyposplenism, IgA nephropathy, primary biliary cirrhosis, sclerosing cholangitis, Sjogren syndrome, Down syndrome and insulin-dependent diabetes mellitus.4-6 Genotyping for CD/DH susceptibility and immunoassays for gliadin, reticulin and endomysial autoantibodies are useful for predicting disease susceptibility and confirming a diagnosis of CD/DH, respectively.

Malabsorption is often accompanied by measurable deficiencies of the fat-soluble vitamins and other general findings related to nutritional deficits such as hypoproteinemia, hypoprothrombinemia and anemia. Many gastrointestinal disorders including gastric and other cancers, inflammatory bowel disease, celiac disease, tropical sprue, intestinal lymphangiectasia, graft versus host disease and a variety of infections and bacterial overgrowth (Whipple disease) can specifically lead to mucosal loss of protein. The cumbersome method of measuring 51chromium-labeled albumin in the stool is inferior to the simple analysis of a1-antitrypsin in the feces. The fact that it is neither reabsorbed nor subject to intestinal proteolysis allows the a1-antitrypsin clearance (grams excreted per 24 hrs multiplied by the ratio of fecal to serum a1-antitrypsin concentrations) to correlate well with the former test.1

In pernicious anemia, the classic example of a specific absorption defect, malabsorption of vitamin B12 reflects lack of the required transport vehicle, intrinsic factor. Acrodermatitis enteropathica, a severe autosomal recessive condition with skin excoriation and pustules, diarrhea and malabsorption, and infections, occurs in infants after weaning due to the lack of a specific zinc absorption factor. Resultant low zinc concentrations can be readily treated with zinc sulfate. Copper deficiency can reflect a similar specific absorption defect in Menkes disease/Occipital Horn syndrome or generalized malabsorption, and can be confused with child abuse. The detection and monitoring of defects of essential trace elements as a result of specific and general malabsorption or other causes was recently reviewed.7

Many conditions presenting with signs and/or symptoms of malabsorption, e.g., acute gastroenteritis and medications, can be associated with secondary intolerance to disaccharides which is often transient and associated with multiple deficiencies of the intestinal disaccharidases. Primary deficiencies of sucrase-isomaltase, lactase, trehalase and primary alactasia are distinct hereditary conditions. Stool pH <5.5 is suggestive of a disaccharidase deficiency, but is invalid in the presence of oral antibiotics, and higher values are not exclusionary. Semi-quantitative (Clinitest tablet, Ames) or quantitative chromatographic analysis demonstrating in excess of 0.5 g/dL of reducing substances in the stool is very helpful, but specific diagnosis requires enzymatic assay on intestinal biopsy material.1 A mutation at nucleotide 3298 in the sucrase subunit of the enzyme complex occurs in sucrase-isomaltase deficiency, and DNA analysis can avoid an invasive procedure.8

Non-invasive analysis of breath hydrogen (H2-BT) is now commonly used to diagnose carbohydrate malabsorption of many causes. H2-BT with D-xylose is simpler and more reliable than the traditional urinary test in celiac disease.7 Overall lactose intolerance is quite common occurring in 10% of Caucasians and over 70% of African-Americans and Asians. A novel automatic sampling system for H2-BT was used in Southern Chinese children to study lactose intolerance with a detection limit of 0.5 ppm H2 and intra-individual coefficients of variation <10%. At a cut-off of 20 ppm rise in H2, 78% of children and 63% of pre-term infants were lactose malabsorbers; whereas, only 18% of term Chinese infants exceeded the cut-off.9 Similarly, a H2-BT is used to diagnose rice carbohydrate malabsorption in Burma where 70% of children are rice-malabsorbers.10

Glucose-galactose malabsorption, a rare autosomal recessive disorder with severe osmotic diarrhea shortly after birth, is due to a missense mutation in the Na+ dependent glucose/galactose cotransporter (SGLT1); a PCR-based assay can be used in prenatal diagnosis.11

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Bacteria that cause cellulitis

Taken from a WebMD Cellulitis ArticleWhat causes cellulitis?

Staph (Staphylococcus aureus) is the most common bacteria that causes cellulitis.

Strep (Group A Streptococcus) is next most common bacteria that causes cellulitis. A form of rather superficial cellulitis caused by strep is called erysipelas; it is characterized by spreading hot, bright red circumscribed area on the skin with a sharp raised border. The so-called "flesh-eating bacteria" are, in fact, also a strain of strep which can in severe cases destroy tissue almost as fast as surgeons can cut it out.

Cellulitis can be caused by many other types of bacteria. In children under six, H. flu (Hemophilus influenzae) bacteria can cause cellulitis, especially on the face, arms, and upper torso. Cellulitis from a dog or cat bite or scratch may be caused by the Pasturella multocida bacteria, which has a very short incubation period of only four to 24 hours. Cellulitis after an injury from a saltwater fish or shellfish (like a fish bite, a puncture from a fish spine, or a crab pinch) can be due to the Erysipelothrix rhusiopathiae bacteria. These same bacteria can also cause cellulitis after a skin injury on the farm, especially if it happened while working with pigs or poultry.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Friday, August 1, 2008

Blood Counts-Manual vs Automated

Blood Counts -- this is a good site—explains the counts and also has info on manual and automated counts… Here is a bit from the link above.

Sources of error in manual WBC counting are due largely to variance in the dilution of the sample and the distribution of cells in the chamber, as well as the small number of WBCs that are counted. For electronic WBC counts and differentials, interference may be caused by small fibrin clots, nucleated red blood cells (RBCs), platelet clumping, and unlysed RBCs. Immature WBCs and nucleated RBCs may cause interference with the automated differential count. Automated cell counters may not be acceptable for counting WBCs in other body fluids, especially when the number of WBCs is less than 1000/μL or when other nucleated cell types are present.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Tuesday, July 29, 2008

Recommendations for dental problems with SDS by Dr. Michael Glogauer:

Recommendations for dental problems with SDS by Dr. Michael Glogauer:

1. Visit your dentist at least every 6 months and more frequently (every 3 months) if oral problems have developed.
2. Discuss home topical fluoride treatments to prevent dental decay.
3. Monitor gums and oral tissues for inflammation and infections (red puffy tissue that bleeds easily) which indicate early periodontal diseases associated with neutropenia.
4. Provide your dentist with Dr. Glogauer’s research paper so that s/he understands the oral problems associated with SDS. (I have the full-text PDF of the paper, if you need it)

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp Notes: Q&A Hem notes

There was a Q&A with Dr. S and Dr. H after their talks. These are my notes from that Q&A session.

I have written down “del 7q is serous” here was mention of del 20q and how it is not as serious as the other clonal abnormalities.

A question came up of using dedicated donors when our SDS kids need transfusions of red cells and platelets. Here is what I wrote down from their answers:

Dedicated donors: DO NOT USE FAMILY DONORS! Relatives as donors increase the risk of graft rejection post transplant.

Donor drive donors have been shown to have a higher risk of infection—volunteer donors are best. When people are *forced* to donate blood products, say because of a co-worker doing a drive, they feel as if they have to give –and will go with infections, etc…..

Random pooled platelets? Or Pherised (sp) platelets to minimize donor exposure? This is becoming less of an issue with newer techniques. Data doesn’t necessarily support this.

Female bone marrow donors—pregnancy (number of) makes a difference—more antigens— if all things are the same in two donors except one is male and one is female w/ pregnancies, they would choose the male.

HLA Loci are located on Chromosome 6. Parents are unlikely to be a match (less than 1-2% chance that parents would be an HLA match for their children)

Growth hormone studies. There are no studies showing increased risk. Talked about the possibility that high doses might have increased risk, but that there really are no studies. There is no data on GH in SDS. Dr. Durie weighed in and said that SDS is a chondrodysplasia meaning that growth plates do not behave themselves & may result in premature fusion of the growth plates (if GH used) no real data, of course & he said that he was very conservative…if the SDS patient was TRULY GH deficient, then he may try it.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp notes: BMT

I wrote down a few things he said that were not on his slides…… just thought I’d share for those interested.

There are 7-8 million people in registry (US) and there are more in Europe. (This is up from the stats in 2006!!! Interesting)

He has a bit on the slides about the regimen…but not with numbers—he said they used this regimen on 50 patients in Cinci (I believe they were all Fanconi’s patients who have the same toxicity issues as SDSers) and they have used it on the 7 SDSers he reports on the slides.

The aplastic anemia patients did better than the MDS and Leukemia patients. The one adult with Leukemia is currently going through transplant again there in Cinci.

The regimen in Cinci begins 3 weeks before transplant—they start the Campath then. (this is on the slides)

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

SDS Article:Myocardial function in patients with Shwachman-Diamond syndrome: Aspects to consider before stem cell transplantation.

Myocardial function in patients with Shwachman-Diamond syndrome: Aspects to consider before stem cell transplantation.
Toiviainen-Salo S, Pitkänen O, Holmström M, Koikkalainen J, Lötjönen J, Lauerma K, Taskinen M, Savilahti E, Smallhorn J, Mäkitie O, Kivistö S.Helsinki Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
BACKGROUND: Early studies have suggested increased risk of fatal cardiac complications in infants with Shwachman-Diamond syndrome (SDS), an inherited bone marrow failure syndrome. Patients undergoing stem cell transplantation (STC) have appeared susceptible to organ toxicity, including cardiac involvement. PROCEDURE: This study assessed anatomical and functional features of the heart in SDS. Eight patients (mean age 24.1 years, range 7-37 years, seven males) with SDS and confirmed SBDS mutations were prospectively assessed for cardiac anatomy, myocardial wall properties, and systolic and diastolic function. The study protocol included conventional echocardiography (n = 8) complemented by exercise Tissue-Doppler echocardiography (n = 7), and by MRI (n = 6). RESULTS: No abnormalities in cardiac anatomy or function were observed in baseline clinical assessment, EKG, or conventional echocardiographic and MRI measurements. Myocardial structure and left ventricular (LV) mass were normal. The maximum isovolumic acceleration (IVA) value during exercise in Tissue-Doppler was significantly lower (P < p =" 0.02)" p =" 0.008)">

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

camp notes: more hematology

These were from a talk by Dr. S..... she gave handouts later. She said the studies are limited.

Evaluation of low blood counts
r/o other treatable causes of low blood counts

anemia-- blood loss, antibodies, erythropoietin levels
neutropenia - infections or medication

G-CSF increases neutrophils and not all patients respond. Indications for using G-CSF:
neutropenia with persistent or serious bacterial infections or fungal infections
neutropenia w/ history of recurrent bacterial/fungal infections, gingivitis or mouth sores
some centers recommend G-CSF prophylactically for persistently low neutrophil counts (<200-500)
need to weigh potential risks
G-CSF potential side effects:
bone pain
enlarged spleen (associated with chronic use)
?osteopenia (seeing it in SCN patients-not sure if it is the underlying disease or from G-CSF)
Anectdotally- kidney problems
Bone marrow exam with cytogenetics should be done prior to initiating therapy with G-CSF. No causal relationship between cytokine therapy and leukemia has been demonstrated to date, but can;t rule it out, either.

Leukemia patients have used G-CSF to get through chemotherapy and have not seen an adverse effect. Not sure if you can extrapolate this to SDS population.

Supportive care for Anemia
Indications for transfusion: symptomatic anemia, fatigue, exercise intolerance, rapid heart rate and breath rate, poor growth

Rough guide: transfuse when hemoglobin is <8 -- this varies from patient to patient.

Risks of transfusion
allosensitizatization: patient develops antibodies against transfused red cells or platelets such that transfused cells are rapidly destroyed (makes transplant harder)
iron overload secondary to red cell transfusion (also makes transplant more difficult) (can use chelating agents)
transfusion reaction
infection (blood borne)
high body iron stores puts you at risk for transplant complications.

supportive care for thrombocytopenia

Indications for transfusion: symptomatic, bleeding, bruising and prophylaxis prior to surgery
20,000 is usually uses, but studies show 5,000-10,000 can be okay. Must consider the patient....for instance, a toddler who is always bonking his head.....transfusion would possibly be considered at a different number.

must also check Vit K levels....low vit K levels with low platelets can cause worse problems. Also, liver function can be a cause of bleeding problems.

Risks of platelet transfusions-- infections

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp notes Dr. S BMT talk/Suggested monitoring of bone marrow failurees:

Dr. S and Dr. H both gave talks on BMT topics. Dr. H had handouts and I don’t think Dr. S did—she did get her hematology 101 or hematology basics handouts to us….. these are my notes from her talks…. If she had hand outs and I missed them….could someone send me a copy?

Here are my notes from her talk on BMT:

One of the questions she had up on the board was: when should transplant be considered?

Donor selection

First choice: HLA matched sibling who does not have SDS.
Be sure to check CBC for siblings. This is particularly difficult in patients without SBDS mutations. This is important! Must look for even subtle changes in CBC or marrow in sibling donors.

Basic principles of HSCT

Cytoreduction (conditioning)
immunosuppression (prevent graft rejection)
myeloablation (make room for new stem cells)
anti leukemic effect (kill minimal residual disease)

Conditioning—this is done by using chemotherapy with or without radiation (TBI) (TBI= total body irradiation)

Acute complications of allogeneic SCT

Endocrine issues are particularly important for children
Increased risk of solid tumors

Reduced Intensity Regimens

Advantage: reduced toxicity of conditioning regimen
Potential problems: not myeloablative (at least not in non-SDS patients)so there is a theoretical risk that premalignant host marrow cells might persist. It might actually be sufficient, but marrow might have SDS marrow left so SDS cells left could cause problems (Dr. Harris addressed this in his talk—not on his handouts--)

Timing of transplant

Factors increasing transplant associated risks
active or occult infections
organ dysfunction
leukemia (need to identify patients at high risk for leukemia)
Age: as patients get older, more side effects/transplant related risks increase
Risk of “preemptive transplant”

Cannot predict whether any individual patient will eventually need a transplant

Transplant planning

HLA matching—get plans in place—it can take up to 6 months to find a donor.
If you have a rare HLA type—start early

Suggested Clinical Monitoring of Bone Marrow Failure

If blood counts are stable (in the normal/mildly low range)and clonal cytogenetics are absent: blood counts every 3-4 months and Bone marrow with cytogenetics every year
Clinical management if new cytogenetic clone is detected or blood counts are falling or rising: counts every 1-2 months, BMB with cytogenetics, then every one-six months, have plans for possible transplant in place. If everything then remains stable, may be able to back off of such frequent monitoring, but the clinical course will determine this.

Dr. S felt that it is important to use a study protocol so that they can learn from the experience. There in Seattle, they are using a new protocol called protocol 2256 using Treosulfan. Treosulfan has been used in SDS patients in Europe. The contact for the Seattle (she flashed this fast) is : lburrough@fhcrc.org

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp notes: Celularity

On Dr. S’s handout I wrote this from her talk:

“Why do we do both BMB and BMA? A looks at individual cells—and we cannot estimate cellularity from the aspirate.” “Interpretation of cellularity needs to be made with caution. It depends on where you sample. “

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp notes: SDS behavioral, social and learning issues

Great talk by Dr. Kerr.

She said that our SDS kids need to have neuropsych evals and to be sure that is what we got….because many psychologists are limited to achievement testing. There are actually colleges who now offer special services….look on the websites for more info (the particular colleges—she did not list them) She gave handouts for her talk, so my notes are short on this one. SDS kids need to be taught specific learning strategies when they have problems… When I get home, I can type in more from the handout—very interesting stuff…I believe the handout said there was a bit more of ADHD in SDS…..

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp Notes: Skeletal and Dental

Skeletal abnormalities—most have them or can develop them. Dysplasia means something that does not form properly. Chondrodysplasia refers to the Metaphyses.

Metaphyseal dysplasia is found in 44-77%
Delayed bone maturation found in up to 100%
Rib +/- thoracic cage abnormalities f found in 32-52%
One study of 15 patients with SDS and SBDS mutations found that skeletal dysplasia was present in all patients & there was no correlation between severity of PI or blood counts
Secondary ossification centers have delayed appearance—they are normal and are just delayed/slow in developing. There is normalization with age.

Metaphyses/Growth Plates

· Widening and irregularity in ribs—this also occurs in Vit D deficiency and Rickets

· There can be progressive metaphyseal irregularity and sclerosis

· Those listed above do not cause pain or problems (Metaphyseal Dysplasia)

SDS patients also often have Osteopenia and wormian bones. These are not a secondary thing due to deficiencies. Careful radiographic follow-up of all patients is warranted. Osteopenia is likely due to low bone turnover…i.e. the bone making cells not doing their job fast enough. Appearance of the gestational mice in the lab with SDS showed normal skeletons—the only difference was the size.

Oral Study Results --SDS patients had more tooth decay and also had more mouth sores than the non-SDS patients in the study. They don’t know if there is anything that can be done to fight osteoporosis. It is primary to the condition. Other things need to be ruled out—just to be sure. Check for hypothyroid and hypoparathyroid. Vit K2 Co factor……

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp Notes: SDS Genetics

Dr. Rommens gave some wonderful talks. As we all know, SDS is autosomal recessive. She went into the inheritance patterns of SDS, etc. The SBDS mutations (when someone had them) are in all the cells of the body. (Constitutional make up of all cells)

I took a lot of notes…… but am only putting in the *important stuff* . SBDS is 1/10th the size of the average gene (I thought this was interesting) There is an SBDS Pseudogene that we all have….yes, everyone has a copy of the SBDS pseudogene. The pseudogene (the SBDS P) has very little functioning protein and is very unstable.

To the best of their knowledge, carriers of SBDS (heterozygous/one gene copy) are unaffected
More than ½ of the SDS patients have the common mutations on exon 2
2 common mutations and 38 known rare mutations now
SDS exists all over the world and some changes are unique to the various populations (again, most have common 2 mutations on exon 2 >50%)
Small number of families with SDS disease and no identified mutations
Families without clinical picture of SDS disease with both hematological and pancreatic dysfunction (at least) do not have mutations in SBDS
One dilemma in SDS is that they do not know the impact of the genetic changes
SBDS is expressed in almost all tissues and they don’t; know why some don’t show symptoms (i.e. variability in disease)
SBDS is highly conserved in all organisms except for bacteria

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp Notes: Hematology

The Hematology session (formerly called Hematology 101)

Some of the talks gave handouts—this was one of them….so I only have a few notes. Once I get home, I will try to add more to this.

Must interpret cellularity in context with the CBC
If the CBC is normal and there is low cellularity, it may be a sampling error
Young children should be quite cellular
Be sure that the marrow is read by those who work with children’s bone marrows…..

There was talk of clones, etc……. can’t draw pictures in email! LOL

CGH is a new genetics test like FISH that paints chromosomes various colors. We were told it is in the research stages—but know one person who has had it done.

MDS/Myelodysplastic syndrome is a highly contested area in IBMFS

People with IBMFS have abnormal marrows and may look like MDS marrows. MDS diagnosis is more complicated in SDS. Adult hem/oncs would say definite MDS…but in SDS it could be normal.

Hypo cellular marrow—mild decrease—wait and watch. The functional test is the blood counts. Over time, if cellularity is dropping and if counts also drop……it is premature to go to transplant with just low cellularity and normal counts.

Notes from Hematology break o0ut session:

I asked about kids without mutations that have been called SDS-like….when looking at the marrow, can you tell they have an inherited bone marrow failure syndrome? Could normal kids have some abnormalities in their marrow.

Yes, normal kids could have something pop up, and that is why repeat marrows are done. i..e if you have an abnormality (mild) in one our of five marrows, then it would be okay for a normal person to have it—but when you have a child who has abnormalities in every marrow, it is a clue to diagnosis.

He explained that of the kids with inherited marrow failure syndromes, 50% are diagnosed…. The other 50% don’t fall into the *named* IBMFS….but they know they have a BMFS because more than one child/person in the family has it

It can be autosomal recessive like SDS or autosomal dominant like SCN or sex linked recessive like DC (only males & skips a generation)

Looking at the marrow, you may not be able to tell that a person has an IBMFS…..

If you have one cell out of 20 with a chromosomal abnormality, it can be considered to be normal. If you have 2 out of twenty, it is a clone. FISH 4% of monosomy 7 is *okay* (tried to paraphrase what he was saying. It is not normal to have 4%, but continued follow up is needed. He went on to explain that sometimes cells can be together and sludge, etc…so that is why follow up is needed.

We talked about iron stores…and there are types of iron stores that you don’t want—especially ringed sideroblasts.

CBC is a late spot for leukemia or MDS. Cannot use CBC in BMFS—must do bone marrow biopsies.

Abnormal clones—even with normal counts must be followed closely with more frequent marrows.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp Sunshine Notes: Gastro, nutrition and SDS--notes from day one

This talk was about the exocrine pancreas, growth and nutrition

In SDS, there are too few Acinar cell- there is fatty replacement.

He gave the definitions of PI and PS

PI (pancreatic insufficient) – needs enzymes

PS(pancreatic sufficient) – mild to moderate pancreatic disease still capable of digesting food.

At diagnosis, 95% of SDS patients are PI ~50% become pancreatic sufficient over the first 4-5 years although starch digestion is still affected.

Monitoring the pancreas. Stool fat losses-72 hr test or the fecal elastase 1 testing, though there are no normal values established in SDS. Testing of blood enzymes (trypsinogen and amylase)

Pancreatic stimulation test has false positive results in 25% & is the most inaccurate--- in the US they don’t collect properly……… us the wrong hormone in the US in particular.

Pancreas testing should be done annually for the first 4-5 years, then if pancreatic function seems to be improved. If not PS by 4-5 years, then it is not likely the SDS patient will become PS

SDS patients may be functioning at 2-3 % of pancreatic function & not need enzymes

Most SDS patients have low serum trypsinogen and those with high serum trypsinogen or normal serum trypsinogen are PS.Growth and nutrition

Malnutrition and FTT are not a problem once feeding properly (enzymes, too) Short stature is the problem. Pushing feeding doesn’t improve the short stature. 80% are lower than the 50th percentile and many are in the 50th percentile. There was a 6’3” patient recently diagnosed….diagnosis came late because of his exceptional growth. So….SDS patients CAN BE TALL. INTERESTING…….. I think this was an interesting point because of comments made about Sean being in the 50th percentile in the past…. VERY validating for those of us with kids who are growing well. I also thought it was interesting that they said growth in SDS children is normal once the enzymes are started/ malabsorption is corrected…. SDS kids tend to grow normally……

Summary—prior to diagnosis FTT and malnutrition, but after diagnosis, these are not a problem SDS patients grow at proper rate once nutritional status improves.


Enlarged liver can be the first clue to a SDS diagnosis. There can be fat in the liver cells. This is usually seen in people with obesity problems—(fat in liver). This seems to go away along with the elevated biochemical tests (liver enzymes). No intervention is usually necessary—Dr. Durie said to keep an eye on it if it is mildly elevated/mildly abnormal.

Fatty changes in the pancreas are not unique to SDS.

Trypsinogen is a precursor to trypsin. Amylase and lipase are not well developed at birth –even in normal kids.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Camp Sunshine Notes:notes from day one-Dr. Durie SDS Clinical DIagnosis

I typed up all the notes I took at the doctor sessions at Camp......I am not a doctor.....and these are just my notes....consult your physician before trying or changing treatment!

We had some interesting talks today! First, Dr. Durie went over the clinical diagnosis of SDS and how it is established, etc. It is difficult to diagnose because there is no one single test and many organs can be affected. There is variability in presentation from person to person. There have been some patients who have had a large liver and that was the single thing that alerted doctors to start looking.

Requirements for diagnosis:

1) exclude other diagnoses

2) exocrine pancreatic insufficiency

3) bone marrow dysfunction

there are many conditions that are like SDS—disorders of the pancreas, various other hematological abnormalities and other growth disorders.

Pancreatic disorders:

CF 95%

SDS 3-5 %

Johanson Bizzard <1%

Pancreatic hypoplasia/dysplasia <1%

Isolated enzyme deficiency <1%

Dr. Durie shared that in all of his many years of practice, he has only diagnosed one case of Johansson Blizzard and 50-60 cases of SDS. Just to give an idea of how rare the other causes of pancreatic insufficiency/ pancreatic disorders are.

The bone marrow problems in SDS are not always easy to detect. Neutropenia can jump up and down.

Skeletal abnormalities.

The main skeletal abnormalities in SDS are:

1) abnormal Metaphyses

2) rib cage abnormalities

3) delayed bone age

4) progressive deformities

5) osteoporosis

6) pathological fractures

skeletal problems may not be present at infancy but manifest at a later age. Short stature is part of SDS not from the malnutrition or malabsorption. Malnutrition is corrected with enzymes and proper feeding. i.e. SDS folks have short stature by nature. Not all SDS people have a growth problem. In fact, SDS patients can absolutely have normal growth. They have recently diagnosed a patient with SDS who is 6’3”—SDS had been overlooked because the patient was so tall and his growth was so normal.

Mutations are found in ~90% of patients. There may be another gene responsible… SDS is a clinical diagnosis—not going to find mutations in everyone and/or don’t always pick up the mutations on the gene.

Obligatory for diagnosis: Exocrine pancreatic dysfunction, bone marrow dysfunction

Common: short stature, skeletal abnormalities, hepatic, behavior

He also mentioned something I thought was interesting (especially since Joseph is in an eczema flare) – a skin rash is common and it is like an allergic eczema rash.

Other things I noted from his talk:

in SDS weight is usually proportional to height—pushing feeding doesn’t make them grow more.
Bone age delay—at puberty bones have longer to grow

Part of SDS

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Saturday, July 12, 2008

Genetics 101

A friend sent this link to me a few months ago. It is a great place to get a basic understanding of genetics. Genetics 101

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Thursday, June 19, 2008

New Booklet Available

Shwachman-Diamond America is pleased to announce that we have a new booklet available. The title is Management of the Hematologic Abnormalities of Shwachman-Diamond Syndrome by Richard Harris, M.D. This booklet is excellent for parents, pediatricians and specialists. If you would like a copy (or copies) of the booklet sent to you, please send your mailing address to shwachmandiamondamerica@embarqmail.com These booklets are FREE to anyone who requests them. Visit the webstie above to request your free booklet.

The booklet includes sections on the following topics:

Management of Neutropenia
Management of Fevers in SDS patients
Antibiotic coverage prior to Dental Work or Surgical Procedures
Management of other Cytopenias
Management of Anemia during Surgical Procedures
Management of MDS
Management of Leukemia
Bone Marrow Transplantation for SDS
And also includes the following:
K-M Survival Plots
Important Contacts
All of us at Shwachman-Diamond America would like to take this opportunity to thank Dr. Harris for all of his hard work and dedication to this project. Thank you, Dr. Harris, from the bottom of our hearts! Your dedication to all of our SDS and SDS-like children is appreciated more than you will ever know.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Tuesday, June 3, 2008

Diagnostic Critera

Bone Marrow Failure: A Child Is Not Just a Small Adult (But an Adult Can Have a Childhood Disease) Click on the link to access the full-text article. The article says this about SDS:

Patients with Shwachman-Diamond syndrome (SDS, OMIM 260400) usually present in early childhood with malabsorption due to pancreatic insufficiency, and neutropenia.25 However, a substantial proportion go on to develop aplastic anemia, MDS, or leukemia.1 These complications may occur in SDS patients who have reached adult age, and thus may have outgrown the care of a pediatric hematologist.
SDS is an autosomal recessive disorder, in which the majority of the tested patients have been found to have mutations in the Shwachman Bodian Diamond syndrome gene (SBDS) located at 7q11.26 Pancreatic insufficiency can be confirmed by demonstration of low serum trypsinogen in young children, although this may improve with age and be normal in adults with SDS. More specific is a low serum isoamylase, which increases in normal children until age 3 but remains low in older children and adults with SDS.27 The diagnosis of neutropenia requires documentation at least 3 times, but may improve with age. About half of the reported SDS patients had metaphyseal dysostosis, and short stature unrelated to malabsorption is a common component of the syndrome. Approximately 40% of the reported patients with SDS developed additional cytopenias, including aplastic anemia, at up to 35 years of age. SDS patients with neutropenia may respond to G-CSF, while pancytopenia may require androgens and consideration of SCT. Unfortunately, the survival after SCT is around 50%, unrelated to whether the donor is a matched sibling or an alternative donor.1 Deaths were related to complications of MDS or leukemia, as well as to cardiotoxicity from cyclophosphamide.
Availability of mutation testing in the SBDS gene may now facilitate consideration of SDS in adult patients with neutropenia or aplastic anemia who were not diagnosed in childhood, but may have a family history or personal history of symptoms consistent with this diagnosis.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Diagnostic Criteria & Minimum Requirements for Follow-up


click on “Shwachman-Diamond Syndrome: UK Perspective

In this article you will see a box that says:

Diagnostic criteria for SDS

Exocrine pancreatic dysfunction (at least one of the


*Abnormal quantitative pancreatic stimulation test

*Serum cationic trypsinogen below the normal range

Abnormal 72 hour faecal fat analysis plus evidence of

*pancreatic lipomatosis by ultrasonographic examination

or computerised tomography


Haematological abnormalities (at least one of the following):

*Chronic (on two occasions at least 6 weeks apart):

single lineage or multilineage cytopenia with bone

marrow findings consistent with a productive defect:

– Neutrophil ,1.56109/l

– Haemoglobin concentration ,2 standard deviations

below mean, adjusted for age

– Thrombocytopenia ,1506109/l

Myelodysplastic syndrome

And a box that says:

Minimum requirements for follow-up:

These should include:

*DNA confirmation of the diagnosis, and offer of

screening to siblings where appropriate

*General clinical review and blood count every

3–6 months

*Serum concentrations of vitamin A, 25-OH vitamin D,

and vitamin E, and prothrombin time six monthly

*Annual review of steatorrhoea and pancreatic enzyme


*A surveillance bone marrow, with cytogenetics, performed

annually or biennially

*Dental review at least annually, ideally every three

months, for preventive treatment, cleaning, and plaque

removal. Oral infections must be treated promptly by

local measures and antibiotics

*Review of growth, pubertal development, nutrition, and

gastrointestinal symptoms at least every six months,

with dietetic involvement.

*x ray examinations every five years to review the

evolution of skeletal abnormalities. If there is evidence

of abnormal long bone alignment, referral to an

orthopaedic surgeon may be appropriate

*Psychometric assessment at or before school entry, and

subsequent educational/psychological help as


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Monday, June 2, 2008

Inherited Pancreatic Disorders of Childhood

From this link: http://www.pancreasfoundation.org/cgi/csNews/csNews.cgi?database=learn_genetics.db&command=viewone&id=1&op=t

Inherited Pancreatic Disorders of Childhood
Peter R. Durie, M.D., FRCPC

There is an extremely wide spectrum of inherited pancreatic disorders in childhood. Depending on the condition symptoms can develop at any time from birth to adulthood. The pancreas makes more than 25 different digestive enzymes which are secreted into the intestine to break down dietary protein, fat and starches into simpler molecules so that they can be absorbed. In fact, the pancreas has a tremendous reserve capacity - more than 95% of the function of the pancreas must be lost before the pancreas fails and symptoms of bloating and maldigestion develop. Children with digestive problems due to failure of the pancreas have to take enzyme replacement therapy with meals as well as additional fat soluble vitamins. The large pancreatic reserve also means that children can have a severe pancreatic problem without experiencing any problems with digestion.
The exocrine pancreas is not fully developed at birth. In fact, all healthy infants show some degree of maldigestion due to the fact that the pancreas is immature and does not have the same ability to produce enough enzymes. This is particularly true for starch and fat digestion. However, the pancreas matures after birth and by two years of age it is functioning in the same way as an adult pancreas. The immature pancreas appears to have no adverse effects on healthy children, but can have a major impact when children become malnourished or very ill.
Cystic fibrosis (CF) is, by far, the most common inherited pancreatic disease of childhood. It accounts for about 90% of childhood onset pancreatic disorders. CF affects many other organs as well and the most common cause of poor health and death is due to progressive lung disease. The CF pancreas begins to get damaged when the affected child is still in the mother’s womb. The small tubes inside the pancreas which allow digestive enzymes to reach the intestine get blocked with mucus and protein and the pancreas became badly scarred and shrinks. Many children with CF have evidence of severe pancreatic failure immediately following birth, and by two years of age 90% of CF are diagnosed - usually with severe malnutrition. Approximately 85% of all people with CF have pancreatic insufficiency and need to take pancreatic enzymes with meals. A lot is known about the genetic cause of CF. The CF gene, which is on chromosome 7, was identified in 1989. The most common CF-disease causing genetic mistake in this gene is called DF508, and is identified in approximately 70% of CF chromosomes worldwide. However, there are more than 1000 additional genetic mistakes in the CF gene, many of which are extremely rare. A lot of research is being done to try to correct the genetic disorder with gene therapy, and to discover ways of getting round the genetic disorder using special drugs.
Shwachman Diamond syndrome (SDS) is the next most common inherited cause of pancreatic failure in childhood. It is much less common than CF and accounts for about 5% of inherited causes of pancreatic disease. This condition also affects other organs including the bone marrow (which makes blood cells), the skeleton and the liver. Children with SDS are very short and are at risk of experiencing severe infections and a particularly severe form of leukemia. Unlike CF, the gene that is responsible for SDS has not yet been identified. However, recent research shows that the SDS gene is also located on chromosome 7. The pancreatic problem is quite different from CF. The cells that make enzymes (acinar cells) don’t develop properly.
After CF and SDS, other causes of inherited pancreatic disease are extremely rare. They include Johansson Blizzard syndrome, Pearson’s bone marrow syndrome and hereditary pancreatitis. It is interesting to note that the hereditary pancreas gene is on chromosome 7 as well. This is a coincidence!
In extremely unusual circumstances a child may be born without any pancreas - which includes both the digestive (exocrine) and insulin producing (endocrine) components of the pancreas. This problem is not compatible with life.

Peter R. Durie, M.D., FRCPCProfessor, Department of PediatricsUniversity of TorontoDivision of Gastroenterology/NutritionHead, CF Research Group, The Research InstituteThe Hospital for Sick Children

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Tuesday, May 27, 2008

eMedicine MDS article updated

Read the full article here

New classification for myelodysplasia

In order to properly treat myelodysplasia syndrome, Down syndrome–related diseases have been reclassified as a separate entity.

Sharon M Castellino, MD, FAAP Wake Forest University Health Sciences
Timothy P Cripe, MD, PhD Cincinnati Children’s Hospital Medical Center
Scott C Howard, MD Cincinnati Children’s Hospital Medical Center

The myelodysplasia syndromes (MDS) are clonal stem cell disorders characterized by progressive cytopenia or cytopenias, usually in the presence of a hypercellular bone marrow and multilineage dysplasia. Usually, all 3 cell lines (myeloid/monocyte, erythroid, megakaryocyte) are involved. Myelodysplasia syndrome is rare in childhood, and most children have a rapidly progressive course. Myelodysplasia disorders have been defined by their predilection to evolve into acute myeloid leukemias (AML), yet not all cases terminate in leukemia.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome.

Bone Marrow Transplant. 2008 May 26.

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome.
Bhatla D, Davies SM, Shenoy S, Harris RE, Crockett M, Shoultz L, Smolarek T, Bleesing J, Hansen M, Jodele S, Jordan M, Filipovich AH, Mehta PA.

[1] 1Department of Hematology Oncology, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH, USA [2] 2Division of Hematology Oncology, Cardinal Glennon Children's Medical Center, St Louis, MO, USA.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for the BM dysfunction seen in patients with Shwachman-Diamond syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced-intensity-conditioning protocol in seven patients with SDS and BM aplasia or myelodysplastic syndrome/AML. The preparative regimen consisted of Campath-1H, fludarabine and melphalan. Four patients received matched related marrow and three received unrelated stem cells (two PBSCs and one marrow). All but one was 8 of 8 allele HLA matched. All patients established 100% donor-derived hematopoiesis. No patient in this cohort developed grades III-IV GVHD. One patient had grade II skin GVHD that responded to systemic corticosteroids and one had grade I skin GVHD, treated with topical corticosteroids. Two out of seven patients developed bacterial infections in the early post transplant period. Viral infections were seen in four out of seven patients and were successfully treated with appropriate antiviral therapy. All patients are currently alive. These data indicate that HSCT with reduced-intensity conditioning is feasible in patients with SDS and associated with excellent donor cell engraftment and modest morbidity.Bone Marrow Transplantation advance online publication, 26 May 2008; doi:10.1038/bmt.2008.151.

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Friday, May 23, 2008

Heel Pain in Children

Heel Pain in Children

Heel pain, unlike the heel spurs, that occur in adults is very uncommon in children. Of those children who do get heel pain, by far the most common cause is a disturbance to the growing area at the back of the heel bone (calcaneus) where the strong achilles tendon attaches to it. This is known as Sever's disease or calcaneal apophysitis (inflammation of the growth plate). It is most common between the ages of 10 to 14 years of age. These are one of several different 'osteochondroses' that can occur in other parts of the body, such as at the knee (Osgood-Schlatters Disease).

To read the rest of the article, click on the link above. It has great information about the formation of growth plates,what causes heel pain, etc.