Shwachman-Diamond disease

Definition: Shwachman-Diamond syndrome (SDS) is an autosomal recessive syndrome characterized by bone marrow failure, pancreatic exocrine insufficiency, skeletal defects, an increased risk of hematologic cancers and abnormal telomere shortening.

Mutations in the gene SBDS are found in >90% of patients with SDS. Indirect evidence suggests that the SBDS gene product may function in RNA metabolism.

There is no evidence of a reduction in telomerase activity in lymphocytes from SDS patients or a physical interaction between the SBDS gene product and the telomerase complex of hTR and hTERT.

Synospsis

 Autosomal recessive
 Short stature
 Low birth weight
 Failure to thrive
 Myocardial necrosis
 Respiratory distress in neonatal period
 Narrow thorax
 Ribs, sternum, clavicles, and scapulae
 Costochondral thickening
 Irregular ossification at anterior rib ends
 Hepatomegaly
 Exocrine pancreatic insufficiency
 Pancreatic lipomatosis
 Severe fat maldigestion
 Steatorrhea
 Nephrocalcinosis
 Delayed skeletal maturation
 Ovoid vertebral bodies
 Coxa vara
 Narrow sacroiliac notch
 Slipped capital femoral epiphyses
 Metaphyseal chondrodysplasia of long bones
 Learning disabilities
 Developmental delay
 Mild mental retardation
 Pancytopenia
 Persistent or intermittent neutropenia
 Anemia
 Thrombocytopenia
 Elevated fetal hemoglobin
 Myelodysplasia
 Acute myelogenous leukemia
 Abnormal liver function tests
 Abnormal fecal fat
 Decreased serum trypsinogen
 Increased susceptibility to infection
 Moderate age-related improvement of pancreatic function
 Broad range in severity of presentation in sibships
 Caused by mutation in the SBDS gene (SBDS, 607444.0001)