A Novel SMPD1 gene mutation, T460P, in a patient with niemann–pick disease type b presenting to a lipid disorders clinic

Abstract

Niemann–Pick disease type B (NPD-B; OMIM 607616) is an inborn error of metabolism where reduced levels of the enzyme acid sphingomyelinase (EC 3.1.4.12) lead to multisystem disease though with survival into adulthood. The natural history of NPD-B is one of progressive hypersplenism and gradual deterioration of pulmonary function. We report a 46-year-old South African man of French-Huguenot descent who presented to a lipid disorders clinic with mixed hyperlipidaemia. Clinical examination and imaging findings revealed the presence of massive hepatospleno-megaly, interstitial lung disease and subclinical atherosclerosis, in the absence of neurological abnormalities. Laboratory testing showed thromboctyopenia, increased liver transaminases and mild hyperbilirubinaemia. Lysosomal enzyme analysis showed markedly reduced acid sphingomyelinase activity, suggestive of NPD. DNA sequence analysis of the SMPD1 gene revealed that he was a compound heterozygote for the previously reported c.1829_1831delGCC (delta R608) mutation and a novel missense mutation c.1378A>C (p.T460P). In summary, we describe a case of NPD-B and report a novel missense SMPD1 mutation, T460P.