title: A novel missense SMPD1 gene mutation, T460P, and clinical findings 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 concentrations of the enzyme acid sphingomyelinase (ASM; 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 describe 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 hepatosplenomegaly, interstitial lung disease and subclinical atherosclerosis; there were no neurological or cognitive abnormalities. Laboratory testing showed thrombocytopaenia, increased liver transaminases and mild hyperbilirubinaemia. Lysosomal enzyme analysis showed markedly reduced ASM 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 (ΔR608) mutation and a novel missense mutation c.1378A > C (p.T460P). In conclusion, we describe the clinical findings of a case of NPD-B with mixed hyperlipidaemia, compound heterozygous for the SMPD1 ΔR608 mutation and a novel mutation, T460P.
authors.affiliation: Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia Lipid Disorders Clinic, Royal Perth Hospital, Perth, Australia.
authors.forename: Yael
authors.initials: Y
authors.lastname: Grasko
authors.affiliation: Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Perth, Australia School of Pathology and Laboratory Medicine, University of Western Australia, Royal Perth Hospital, Perth, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.affiliation: Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia Lipid Disorders Clinic, Royal Perth Hospital, Perth, Australia School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Perth, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
authors.affiliation: Lipid Disorders Clinic, Royal Perth Hospital, Perth, Australia School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Perth, Australia Department of Internal Medicine, Royal Perth Hospital, Perth, Australia gerald.watts@uwa.edu.au.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D006579:Heterozygote; D006801:Humans; D052439:Lipid Metabolism Disorders / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D052537:Niemann-Pick Disease, Type B / Q000209:etiology / Q000235:genetics*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase
keywords: Lipids; genetics; inborn errors of metabolism