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.