Discordant Endocrinopathy in a Sibling with Shwachman-Diamond Syndrome

Abstract

Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder that is characterized by exocrine pancreatic insufficiency, haematological dysfunction and skeletal abnormalities. However, there are many solitary sporadic cases in which their organs or functions may be showing a wide range of abnormalities and symptoms [1]. SDS usually has exocrine pancreatic insufficiency, and rarely shows endocrine pancreatic insufficiency. We experienced a rare case of SDS with diabetes mellitus (DM). The patient with short stature and skeletal abnormalities showed neutropenia, pancreatic insufficiency and chronic hepatitis. Exocrine pancreatic insufficiency and neutropenia improved with age. Her brother and uncle developed similar symptoms. We investigated the endocrine pancreatic function and genetic analysis of the siblings. A previously healthy child at the age of one was admitted because of pneumonia. Examination revealed liver dysfunction and the pathology of her liver biopsy showed chronic hepatitis at the age of two. She was admitted several times because of pneumonia and cyclic neutropenia. After reaching the age of three, her neutropenia improved gradually. Short stature, decayed teeth, narrow chest (short ribs with broadened anterior) and hirsutism were seen detected and she had frequent soft stool until she was 3 years old. At the age of five, she was admitted to our hospital because of loss of body weight and hyperglycaemia, and was diagnosed as insulin-dependent diabetes mellitus (IDDM) [blood sugar level was 560 mg/dl. HbA1C and fluctosamine were elevated and 1, 5AG (1,5-anhydroglucitol) was decreased. Urinary and blood C-peptide revealed low levels. Anti-insulin and GAD (glutamic acid decarboxylase) antibodies were not detected]. Her pancreas showed hyperechogenic patterns by echogram, atrophy and fatty changes by abdominal CT (Fig. 1A). Pancreozymin–secretin (PS) test and pancreatic function diagnostant (PFD) test were both of low response. Bone marrow showed hypoplasia of all the three characters and fatty changes without any elevation of blastic cells. After admission she was treated with insulin, and improved gradually. She has been in good control with insulin, given three times a day, which could be reduced to two times a day. She has had pneumonia with mild neutropenia once without the need of admission.