Shwachman-Bodian-Diamond syndrome (SBDS) is a rare autosomal recessive inherited disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction with increased risk of developing leukemia, skeletal malformations and short stature. After cystic fibrosis, SBDS is the second most common cause of exocrine pancreatic insufficiency in childhood. Hematologic disorders include neutropenia with defective chemotaxis, moderate thrombocytopenia and anemia, and increased fetal hemoglobin concentration. These disorders increase in severity, leading to aplasia in 25% of cases. As long as neutropenia is moderate and asymptomatic, management is limited to nutrition (pancreatic enzymes, nutrients, vitamins). Sometimes therapy with the hematopoietic growth factor G-CSF (granulocyte colony-stimulating factor) is beneficial. Patients have an increased risk of developing secondary leukemia (usually AML).
Approximately 90% of SBDS patients have loss-of-function mutations in the SBDS gene on chromosome 7. Approximately 75% of causative variants are caused by gene conversion with the pseudogene SBDSP1. SBDSP1 is a non-functional copy of the SBDS gene with 97% identical sequence. In about 95% of cases, exon 2 and intron 2 are affected.
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