Shwachman-Diamond Congress Notes day 1

The first day of the Congress as very intereting. The first half of the day was on the Clinical features of Shwachman-Diamond Syndrome. Keep in mind that rhese are my notes from the Congress! I hope I got everything correct, but ..... if you'd like more specific info, please contact me.

Dr. Durie discussed pancreatic involvement in Shwachman-Diamond, the pancreatic phenotype.

A Shwachman-Diamond diagnosis includes bone marrow dysfunction, exocrine pancreas dysfunction. Must exclude other diagnoses and prove pancreatic dysfunction and bone marrow failure.

To assess the pancreas - stim test, 72 hour fecal fat, serum fat soluble Vitamns A, E and 25-OHD. Serum enzymes should be run, trypsinogen, isoamylase and fecal elastase is also helpful.

Can remove up to 95% of normal pancreas and still have normal function. A person can have 3% function in SDS and not require enzymes.... Have to lose 98% of function in SDS in order for pancreatic dysfunction to show up.

7% fat malabsorption is normal. Stim tests by endoscope should not be done. Too many false positives.


SDS consensus guidelines by Dr Kuijpers. Consensus doesn't mean everyone has to agree, but they understand they are on the same page. Must exclude CF by normal sweat test, have a cytopenia and exocrine pancreatic dysfunction. Neutropenia is the most common hematologic abnormality. Molecular diagnosis-SBDS gene mutation is helpful. Genetic testing has some pit falls. Neutropenia must be present 2 times in 3 months or hypo productive cytopenia detected in 2 occasions in 3 months. Pancreatic Insufficiency is diagnosed by fecal elastase, serum enzymes, etc. 10% of SDSers do not have SBDS mutations. Delayed umbilical cord detachment is common in Shwachman-Diamond.


Imaging in SDS - brain cognition, pancreas liver, heart gut. Abdominal CT is equal to radiation of 400 chest xrays

Hem abnormalities in Shwachman-Diamond by Dr. Shimamura
Marrow cellularity is patchy, so can be variable, so cellularity needs to be interpreted in conjunction with counts. Severity of BMF in Fanconi's we know:

Mild --- neutropenia 1000-1500 platelets 50-150, hemoglobin less than 8

MDS is defined cytogenetic clones and dysplasias. Males with Shwachmn-Diamond more likely to develop MDS. Can have MDS because of clones but without dysplasia. dr Shimamura calls MDS in Shwachman-Diamond high risk with increased blasts between 5 and 20 percent.

MDS in Shwachman-Diamond-mean age is 8 and for AML is 21. Male risk for AML is even higher than for MDS in Shwachman-Diamond Syndrome. Usually, we treat leukemia prior to transplant, but in bone marrow failure, it can cause more problems. It causes increased transplant morbidity in SDS so we have to be careful. In SDS cytopenias during Chemotherapy are prolonged.

What are early markers of elevated leukemia risk? Most common clones mono 7, i(7q) del 20q. No cases of i(7q) known to develop leukemia in Shwachman-Diamond.

Co morbidities in SDS transplant ....liver, cardiac, priorminfections, blood products. Dr. Shimamura said we could argue that all Shwachman-Diamond Syndrome could be low grade MDS.

Dr. Kerr- Understanding Neuropsychological Functioning in Shwachman-Diamond Syndrome. There is an article published that mentions Delayed myelination in Shwachman-Diamond Syndrome- KA Ida et al 2005 It had been demonstrated that individuals with Shwachman-Diamond are at risk for neurocognitive and neuropsychiatric issues. Most specifically, intellectual function. Weakness in visual processing and attention. And weakness in executive function.

Registry update. Approximately 90 patients in registry. (not exactly sure of the number-may have written down the wrong number) -- SDS-Like is now being called SDS indeterminate by the Shwachman-Diamond Syndrome registry folks.

101 Shwachman-Diamond patients entered into French registry (with SBDS mutations). They conclude that a profound cytopenia at baseline should be considered high risk of leukemia.

Dr.Rommens- genetics and disease models of Shwachman-Diamond.

Ribosomal diseases are SDS,DKC, DBA, and 5 q syndrome
Complete loss of SBDS is not compatible with life. It is essential for life. SBDS is expressed in all cells. Have produced mice which produce no SBDS protein.

Shwachman-Diamond is a ribosomopathy. Talk on Drosophilia fly by Dr Tan. SBDS is required for growth of the drosophila fly----

Talk by Elaine Provost saying Shwachman-Diamond is a p53-independent Ribosomopathy.

Median Survival Age for SDS Patients

From the eMedicine Article on Shwachman-Diamond Syndrome:

Alter et al (1998) report that the projected median survival age is older than 35 years for all patients with SDS. For those patients whose course is complicated by aplastic anemia, the median survival age is 24 years, while those patients whose course is complicated by leukemia have a median survival age of 10 years.

More on SDS Life Expectancy from Literature

Another article that lists the median survival as age 35 is titled: Bone marrow failure: a child is not just a small adult (but an adult can have a childhood disease). You can access the full-text article from this link. Click on the title (4th one down) Shwachman-Diamond America Medical Articles

For more resources to quote from, you can also see the new article titled: Shwachman Diamond Syndrome: an emergency challenge which can be accessed at this link: Shwachman-Diamond Syndrome Articles it is the second article on the page—click on the title and the PDF full text will appear. Here is a quote from this article (P 12):

“Alter et Al (1997) reported a median survival age older than 35 years for all patients with SDS. For those patients whose course is complicated by Aplastic anemia, the median survival age is 24 years, while those patients whose course is complicated by leukemia have a median survival age of 10 years.”

Life Expectancy in Shwachman-Diamond Syndrome

If you are looking for the words “Life expectancy” you will likely not find it in medical literature…BUT you can find many articles that list median survival and various other stats. Are you reporting for a statistics class or are you doing a project for another class? In Stats, median range is usually given---

In fact, the median survival is listed in literature as 35 yrs. See the article titled: Diagnosis, Genetics, and Management of Inherited Bone marrow failure syndromes which can be accessed from this link: Shwachman-Diamond Syndrome Medical Articles This article includes a section on SDS that says (page 36)

“…and many patients evolve to Aplastic anemia, MDS or Leukemia. The median age for the latter in the literature reports is 18 years, and the age dependant cumulative probability of leukemia is greater than 70%.”


There is a chart in this article on page 30 that lists the following for SDS:


Age at cancer, median (range)-----------------18 (2-43)

Cumulative probability (%) of cancer by age 40-50-----71

Projected median survival age*------------------------35

% alive or dead greater than or equal to 16 y of age----22

Shwachman-Diamond Syndrome and Bone Marrow

From this website: http://www.pathologyoutlines.com/bonemarrow.html

Shwachman-Diamond syndrome and bone marrow

Rare autosomal recessive childhood stem cell disorder with peripheral cytopenia (particularly neutropenia), ineffective hematopoiesis, and variable marrow cellularity; also pancreatic insufficiency with pancreatic fatty infiltration

Frequency develop aplastic anemia, myelodysplastic syndrome or acute myeloid leukemia
May be a myelodysplastic disorder from inception (Archives 2002;126:1157)

Laboratory: low serum isoamylase

Case reports: with successful bone marrow transplant (Eur J Pediatr 1999;158:995)

Micro-bone marrow: hypocellular; scattered mild dysplastic changes in all cell lines; may have prominent hematogones (Archives 2000;124:1379)

Micro images: histology and immunohistochemistry; various images

Positive stains: p53

Molecular: mutations in Shwachman Bodian Diamond syndrome gene in 90% (Blood 2004;104:3588)

References: Blood 1999;94:3048, Archives 2002;126:452, OMIM 260400, eMedicine, Wikipedia

Fetal Hemoglobin

If you read medical literature about Shwachman-Diamond Syndrome, you'll find that many patients with SDS have elevated fetal hemoglobin.

There are 6 different types of hemoglobin (I cannot create the symbols on my computer for them all - mostly Greek letters)

Each one of these different hemoglobins has a different globin chain -- and the chains each are coded by different genes which are "turned off or "turned on" during the different stages of development. During the first 3 mos of embryonic development Hemoglobin Portland is produced(blood cells are produced in the yolk sac at this stage). As the red blood cell making (erythropoiesis) changes to the liver and the spleen-- hemoglobin F appears. When erythropoiesis shifts to the bone marrow during the first year of life, the adult hemoglobins (Hb A and Hb A2) begin to be produced.

Info gathered from several physiology books I have lying around here at home.

Calculating an ANC

After calculating an ANC for so many years, it seems like second nature to me. Neutropenia is the most common hematological abnormality in Shwachman-Diamond Syndrome. Many of the familys that contact Shwachman-Diamond America ask , "How do you calculate ANC?"

I have a page on our family website dedicated to neutropenia. I built this page many years ago in hopes that it would help people surfing the web to understand what neutropenia is, what causes neutropenia and how to figure out what a person's absolute neutrophil count is. Visit the hyper links in this post for more information on neutropenia and its causes. Here is the basic formula for calculating the absolute neutrophil count:

To obtain the Absolute count, one must multiply the relative value of each type of cell (neutrophils in our case) by the total WBC count. If a person has a total WBC of 6,000 and his differential shows 30% neutrophils, to figure the Absolute Neutrophil Count (ANC) we multiply 6,000 by 30% to arrive at an ANC of 1800.

Shwachman-Diamond Syndrome and Dental Issues

Life along SDS Highway 101 often has stops at the dentist. We get off at that exit tomorrow! Children with Shwachman-Diamond Syndrome often have dental abnormalities. Enamel defects are very common. Because SDS children have neutropenia and neutrophil chemotaxis defects, gingivitis, mouth ulcers and oral infections are also another common finding. I have several neutropenia and SDS dental articles that I have found to be very interesting. My boys' x-rays are published in one SDS dental article because of a rare finding they have.

They have both had internal tooth resorption on molars that were in perfect condition. No cavities, no defects or anything. They lost these molars 4-5 years early because they were literally eaten from the inside out. When we contacted centers that treated SDS patients around the world, we were told that they were the only two SDS patients they knew of who had internal tooth resoption. This prompted the doctors to publish their x-rays in an article.

Internal tooth resorption is not the same as root resorption that occurs when a child loses a baby tooth. The adult tooth pushes through, causing the roots of the baby tooth to be reabsorbed--this is completely normal.

Tomorrow, I bring all three of my boys to the dentist. I'm hoping that the appointments go well and we don't find anything odd. Just another day along SDS Highway 101.

What is Shwachman-Diamond Syndrome?

Shwachman-Diamond Syndrome (SDS), first described in 1964, is a rare, genetic (autosomal recessive), multi-systemic disorder affecting the pancreas, bone marrow, and skeleton. The most common symptoms are pancreatic dysfunction (malabsorption), low neutrophil count and short stature. Other organs may also be involved in some SDS patients. Shwachman-Diamond Syndrome affects people differently and not all people with SDS have all of these symptoms. In Infancy, the first symptoms are usually loose, foul smelling, greasy stools and failure to gain weight and grow normally. The pancreas fails to produce the enzymes essential to digest food properly. Because of the exocrine pancreatic dysfunction (malabsorption), the child does not absorb enough nutrients, most commonly the fat-soluble vitamins, to grow and develop normally. Oral enzyme replacement therapy helps these children to digest their food, but many still need to take special vitamin supplements. Improving nutritional status does not necessarily improve the growth of children with Shwachman-Diamond Syndrome.

The bone marrow, where blood cells are produced, is also affected in Shwachman-Diamond Syndrome. White blood cells, which fight infection, are most commonly affected. Neutropenia is the most common hematological abnormality in SDS, though all blood cell lines may be affected. Anemia and blood clotting problems are also common in SDS patients. Because of the bone marrow dysfunction, these children are at a greater risk of developing life-threatening infections. Shwachman-Diamond Syndrome is considered to be a bone marrow failure syndrome, because up to 30% of these children will develop leukemia or aplastic anemia.