Shwachman-Diamond syndrome mimicking mitochondrial hepatopathy

Abstract

Shwachman-Diamond syndrome (SDS) is a genetic disorder caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. The syndrome is characterized by multiorgan dysfunction primarily involving the bone marrow and exocrine pancreas. Frequently overlooked is the hepatic dysfunction seen in early childhood which tends to improve by adulthood. Here, we report a child who initially presented with failure to thrive and elevated transaminases, and was ultimately diagnosed with SDS. A liver biopsy electron micrograph revealed hepatocytes crowded with numerous small mitochondria, resembling the hepatic architecture from patients with inborn errors of metabolism, including mitochondrial diseases. To our knowledge, this is the first report of the mitochondrial phenotype in an SDS patient. These findings are compelling given the recent cellular and molecular research studies which have identified SBDS as an essential regulator of mitochondrial function and have also implicated SBDS in the maintenance of mitochondrial DNA.

Keywords: SDS; elevated transaminases; failure to thrive.

Figure 1

Patient's physical features. (A) Photograph featuring minor facial dysmorphisms: broad forehead with frontal upsweep of hair, epicanthic folds, and stellate irises. (B) Photograph featuring bell‐shaped thorax.

Figure 2

Pathology specimens from pediatric Shwachman–Diamond syndrome liver biopsy. (A) Representative hematoxylin and eosin stained high‐magnitude magnification (×40) of liver biopsy demonstrating lipid droplets (asterisks); inset magnified for clarity. (B) Representative electron microscopy demonstrating intrahepatic lipid droplets (asterisks) and numerous small mitochondria (arrowheads); inset magnified for clarity.