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
Transfusion
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

Immunologic
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.


LIVER

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

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

Transient Aplastic Crisis - Parvo B19

http://sickle.bwh.harvard.edu/aplastic_crisis.html




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

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:

Description
History
Diagnosis
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
References
Glossary
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

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

http://www.shwachmandiamondamerica.org/SDSarticles.html

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

following):

*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

AND

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

supplementation

*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

required



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

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