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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2017

Open Access 01-12-2017 | Review

Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)

Authors: Margaret M. McGovern, Ruzan Avetisyan, Bernd-Jan Sanson, Olivier Lidove

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

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Abstract

Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations. Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). NPD A is associated with a uniformly devastating disease course, with rapidly progressing psychomotor degeneration, leading to death typically by the age of 3 years, most often from respiratory failure. In contrast, the clinical phenotype and life expectancy of patients with NPD B may vary widely. Almost all patients have hepatosplenomegaly and an atherogenic lipid profile, and most patients have interstitial lung disease with progressive impairment of pulmonary function and hematologic abnormalities including cytopenias. Other common clinical manifestations include liver dysfunction, heart disease, skeletal abnormalities and growth delays. Some patients with ASMD who survive beyond early childhood have intermediate phenotypes (variant NPD B) characterized by combinations of non-neurologic and mild to severe neurologic symptoms. The physical and psychosocial burden of illness in patients with NPD B is substantial. Common symptoms include shortness of breath, joint or limb pain, abdominal pain, bleeding and bruising. The disease often leads to chronic fatigue, limited physical or social activity and difficulties in performing daily activities or work. Many patients die before or in early adulthood, often from pneumonia/respiratory failure or liver failure. Available treatments are limited to symptom management and supportive care. An enzyme replacement therapy currently in clinical development is expected to be the first treatment addressing the underlying pathology of the disease. Early diagnosis and appropriate management are essential for reducing the risk of complications. While knowledge about ASMD is evolving, more evidence about ASMD and the natural history across the disease spectrum is needed, to improve disease recognition, timely diagnosis and appropriate disease management.
Footnotes
1
There are currently two numbering systems for SMPD1 mutations as a result of two reference sequences (GenBank Accession Numbers NM_000543.4 and M81780.1) that differ by a length polymorphism within the signal peptide region. Reference to mutations should refer to the appropriate reference sequence for clarity; in this paper, the NM_000543.4 sequence was used.
 
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Metadata
Title
Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)
Authors
Margaret M. McGovern
Ruzan Avetisyan
Bernd-Jan Sanson
Olivier Lidove
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-017-0572-x

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