Niemann-Pick Disease, A Rare Cause of Hepatomegaly and Failure to Thrive in Infancy

Abstract

Purpose: Niemann-Pick disease type A is a disorder caused by mutations in the sphingomyelin phosphodiesterase-1 gene (SMPD1). It is characterized by a primary deficiency of acid sphingomyelinase activity. A male infant was born at 36 6/7 weeks gestation. His birth weight was 2.352 kilograms. Apgars were 8 and 9 at 1 and 5 minutes respectively. His neonatal course was complicated by vomiting and abdominal distension and indirect hyperbilirubinemia which resolved within the first week. The infant initially grew along the 5th percentile for weight. The patient was admitted to the Avera McKennan Children's Hospital at seven weeks of age due to fever. Blood, urine and CSF cultures were all negative at the time of discharge. Viral studies on the CSF including CMV, enterovirus and herpes were negative as well. At two months of age his weight and height parameters were below the third percentile. At 5 months of age, the infant developed non-tender anterior cervical lymphodenopathy less than 1 cm diameter in size. He was also noted to have hepatosplenomegaly, elevated serum transaminases, and continued to have failure to thrive. Abdominal ultrasound demonstrated hepatosplenomegaly. No hepatic or splenic lesions were seen. The hepatic and splenic vessels were patent with no evidence of portal hypertension. Liver and lymph node biopsies demonstrated prominent foamy histocytic accumulation with lysosomal myelin-like inclusions in portal tracts and sinusoids identified by electron microscopic examination. The residual acid sphingomyelinase activity in peripheral blood leukocytes was markedly decreased consistent with Niemann-Pick disease Type A.Figure: Liver biopsy showing foamy histiocytes.Figure: Hepatosplenomegaly in Niemann-Pick disease.Table: Table. Liver function tests in Niemann-Pick disease