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Shwachman Diamond Syndrome

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Shwachman Diamond Syndrome (SDS) is a rare disorder with the three most common symptoms being bone marrow failure, pancreatic insufficiency, and skeletal abnormalities (Dror, 2005). Bone marrow failure is the result of damaged hematopoietic stem cells and pancreatic insufficiency results from defects of acinar cells. According to Smith et al. (1996), other symptoms of the disorder include immune dysfunction, liver disease, renal tubular defects, diabetes, psychomotor retardation, neutropenia, anemia, thrombocytopenia, and a susceptibility to leukemic transformation. The age of onset of SDS can vary from the neonatal period to childhood and although the diagnosis tends to be delayed due to the rarity of the disorder, the disease is rarely diagnosed …show more content…

The affected gene of this disorder is the Shwachman Bodian Diamond Syndrome gene located on chromosome 7 with an interval of 1.9 cM at 7q11 (Boocock et al., 2002). The SBDS gene encodes a protein that is predicted to be 250 amino acids in length; however, this amino acid sequence has no homology to any known domains and there have not been any signal peptides detected (Boocock et al., 2002). The most common mutation that causes the disorder is a conversion mutation; frameshift, missense, and silent mutations have also been described. According to Boocock et al. (2002), the two most common mutations occur in exon two and are a thymine adenine to a cytosine thymine change at position 183 and an eight base pair deletion at the end of the exon. There is a pseudogene copy of SBDS located distally to the original gene that is the cause of the conversion mutations. These mutations can lead to a premature end of the encoded protein. Another unrelated mutation occurs in chromosome 20. In SDS patients, it has been found that there is a deletion of the long arm of chromosome 20 which leads to a loss of the EIF6 gene which functions in ribosome biogenesis (Vali et al., 2013). These mutations only occur in 90% of SDS patients; it has not been determined whether there is a different type of SDS that does not have a mutation or if these symptoms could be the cause of other undefined disorders (Myers et al., …show more content…

These marrow failure syndromes include aplastic anemia, myelodysplastic syndrome, and acute myeloid leukemia all of which can only be cured with HSCT (Latour et al., 2015). If HSCT is not performed, the only remaining treatments are supportive. The process of HSCT is as follows: one and a half liters of stem cells and fluid are collected from the donor patient, usually from the pelvis, by needle aspiration. The transplant patient has to be admitted to a hospital ten days before the procedure to receive saline fluids, a central line, intensive chemotherapy, and immunosuppression. The chemotherapy can be with or without radiation and is used to ensure death of all of the damaged stem cells. Immunosuppression, by medicines or plasmapheresis, is used to ensure that the body does not reject the donor stem cells. After these steps have been completed, the donor stem cells will pass through a filter to remove bone fragments and fat cells and will eventually travel into the receiving patient’s bone marrow. The patient will stay in a sterile environment and will continue to receive transfusions until engraftment occurs. The patient’s platelets and red blood cells will fully recover in two to six months (Silverman et al., 2007). A case study done in 2005 reported that there had only been 24 stem cell transplantations for SDS patients. Of the 24

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