Title: Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients
Authors: Hollak, C E M ×
de Sonnaville, E S V
Cassiman, David
Linthorst, G E
Groener, J E
Morava, Eva
Wevers, R A
Mannens, M
Aerts, J M F G
Meersseman, Wouter
Akkerman, E
Niezen-Koning, K E
Mulder, M F
Visser, G
Wijburg, F A
Lefeber, D
Poorthuis, B J H M #
Issue Date: Nov-2012
Publisher: Academic Press
Series Title: Molecular Genetics and Metabolism vol:107 issue:3 pages:526-533
Abstract: Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12months for pulmonary function tests, 6minute walk test (6MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6years, with some decline in pulmonary function and 6MWT. Bone marrow fat fractions were decreased, indicating the presence of storage macrophages. Lung involvement was not related to the extent of visceromegaly, cytopenia or bone marrow involvement. In conclusion, in NPD-B patients pulmonary disease is the most debilitating feature. Disease manifestations are mostly stable in attenuated patients. Bone marrow infiltration is a less prominent feature of the disease.
ISSN: 1096-7192
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hepatology
Laboratory for Clinical Infectious and Inflammatory Disorders
× corresponding author
# (joint) last author

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