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Acid sphingomyelinase‐deficient Niemann–Pick disease: Novel findings in a Greek child
Author(s) -
Fotoulaki M.,
Schuchman E. H.,
Simonaro C. M.,
AugoustidesSavvopoulou P.,
Michelakakis H.,
Panagopoulou P.,
Varlamis G.,
NousiaArvanitakis S.
Publication year - 2007
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-007-0557-3
Subject(s) - acid sphingomyelinase , lethargy , niemann–pick disease , medicine , lysosomal storage disease , cardiomyopathy , sphingomyelin , pathology , gastroenterology , cystic fibrosis , endocrinology , disease , heart failure , cholesterol
Summary Niemann–Pick Disease (NPD) is a heterogeneous group of autosomal recessive disorders characterized by progressive accumulation of sphingomyelin and cholesterol in lysosomes. Six types of NPD have been described based on clinical presentation and involved organs. The primary defect in NPD types A and B is a deficiency of lysosomal acid sphingomyelinase (ASM). We present a case of a 5‐year‐old boy with type B NPD who had severe clinical manifestations, including heart involvement. He was first admitted to the hospital at 2 months because of vomiting, refusal to feed, lethargy, hepatomegaly and mild transaminasaemia. Liver biopsy at 12 months showed lipid accumulation and fibrosis. Investigations for lysosomal storage disorders revealed increased plasma chitotriosidase (549 nmol/h per ml, normal value 0–150). At 18 months, no detectable ASM activity was observed in cultured fibroblasts (normal range 23–226 nmol/h per mg protein) confirming NPD B. Pulmonary involvement was detected with high‐resolution computerized tomography which revealed reticulonodular infiltrations and thickening of the interlobular septa. At 2 years growth retardation and kyphosis were noted. At 2.5 years he manifested neurodevelopment regression, indicating CNS involvement. Cardiac involvement (grade III mitral valve insufficiency) developed at 4 years and heart failure at 5 years. Genetic analysis revealed two mutations: a H421Y mutation that is common in Saudi Arabian and Turkish patients, and a W32X mutation, which has been found in other Mediterranean patients.