ShwachmanDiamond

Shwachman-Diamond syndrome is a rare inherited disorder characterized by bone marrow failure, pancreatic exocrine insufficiency, and skeletal abnormalities. It was first described in the 1960s by Dorothy Shwachman and others. The condition is a form of ribosome biogenesis disorder and presents with a spectrum of features that may evolve over time.

Most cases result from biallelic mutations in the SBDS gene, located on chromosome 7, inherited in an autosomal recessive pattern. In a minority of patients, SDS-like phenotypes can arise from defects in other genes involved in ribosome assembly, such as EFL1, DNAJC21, and SRP54. The SBDS protein is involved in ribosome maturation and function; disruption leads to impaired formation of blood cells and pancreatic cells, contributing to the characteristic findings.

Clinical features commonly include exocrine pancreatic insufficiency with malabsorption and poor weight gain, leading to growth retardation. Skeletal abnormalities, such as metaphyseal chondrodysplasia and short stature, are frequent. Bone marrow failure, often manifesting as neutropenia, increases susceptibility to infections and may progress to myelodysplastic syndrome or acute myeloid leukemia over time. Additional issues may include immune dysfunction and recurrent respiratory infections.

Diagnosis relies on clinical suspicion supported by laboratory and genetic testing. Low pancreatic elastase and fat-soluble vitamin deficiencies indicate exocrine pancreatic insufficiency, while peripheral blood shows neutropenia or other cytopenias. Definitive confirmation comes from SBDS sequencing; broader panels may identify related ribosome biogenesis defects.

Management focuses on supportive care: pancreatic enzyme replacement, fat-soluble vitamins, nutritional support, and infection management. Hematologic interventions, including growth factors or transfusions, are used as needed, with hematopoietic stem cell transplantation reserved for severe marrow failure or progression to MDS/AML. Regular surveillance for hematologic and pancreatic complications is recommended. The prognosis varies with severity and responses to therapy.