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

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