Day 2 and 3 of the SDS Congress were very scientific! Some data we cannot publish because the authors have not yet published! There are great things happening in Shwachman-=Diamond Research.
Wednesday begain with discussions on SBDS function. Most of it focused on the ribosomal subunits. The question, is SDS a ribosomopathy?, was the biggest topic of discussion on day 2 of the conference. 60 subunit biogenesis is affected. Researchers postulate that thee is an issue with making ribosomes and with their function.
The second part of the second day focused the function of SBDS in hematopoiesis and leukemia and we had the annual Jason Bennette memorial speaker who spoke about niche dynamics (the microenvironment of the marrow). The last part of the afternoon was dedicated to organ development and failure.
Vdac1 mitochondrial voltage gated anion channel. Thought to be a mito permeability pore. Do mito function properly in SDS? This was a question that was brought up.... and one I find interesting since my boys have been diagnosed with secondary Mitochondrial Disease.
A Doctor from Cambridge spoke and said that SDS is a disorder of ribosome maturation. This echoed earlier speakers.
Dr. Shimamura gave a talk on SBDS in ribosome biogenesis and mitotic spindle stabilization:
SBDS and mitosis. Increased incidence of abnormal mitotic cells. Cell eventually dies. Stabilization of spindles, improves hematopoiesis
We had a speaker who spoke about ADHD, but it was not specific to Shwachman-Diamond Syndrome or SDS studies. This was followed by several presenters who spoke about pancreas development with SBDS. Dr. Domain spoke about stem cell models of cardiac development and disease (not specific to SBDS). His presentation was excellent, even showed some of the cardiac stem cels in motion! Crontracting.
This morning (Thursday) we continued with organ development and failure. The focus was on skeletal defects and development of dysplasia.
Late morning discussions were aimed at using humn pluripotent stem cells in SDS, and the last speaker was Dr. de Figueiredo from Texas A & M and he spoke about the effects of HDAC inhibitors on disease models of Shwachman-Diamond Syndrome.
ADHD talk
4% of population affected
skeletal variability is quite large.
infancy and childhood delayed appearance f ossification centers
mid childhood slow dev of ossification centers.
osteoporosis
Showing posts with label SDS Congress Notes. Show all posts
Showing posts with label SDS Congress Notes. Show all posts
Thursday, June 30, 2011
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.
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.
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