JIM 2024;
1 (4): e634
DOI: 10.61012_202411_634
Acid sphingomyelinase deficiency: a complex and rare disorder that needs clinicians’ awareness
Topic: Inherited Metabolic Diseases in Paediatric Age
Category: Review
Abstract
Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease types A and B, is an autosomal recessive lysosomal storage disease caused by mutations in the SMPD1 gene. These mutations lead to reduced activity of the lysosomal enzyme acid sphingomyelinase (ASM), resulting in the progressive accumulation of sphingomyelin and other glycosphingolipids in multiple tissues and organs.
Storage of undegraded substrates triggers a complex and only partially understood cascade of secondary events, culminating in a progressive multisystem disease with a broad clinical spectrum characterized by neurological and visceral manifestations. Three main phenotypes have been traditionally identified: a severe infantile neurovisceral form (or Niemann-Pick type A), an intermediate chronic neurovisceral form (intermediate Niemann-Pick A/B; Niemann-Pick B variant), and a chronic visceral form (Niemann-Pick type B).
The rarity of ASMD and the resulting lack of clinician awareness contribute to frequent misdiagnoses and delays in diagnosis despite advancements in diagnostic tools. Given the recent introduction of alpha-olipudase enzyme replacement therapy, which may provide substantial clinical benefits when initiated early, timely diagnosis has become crucial.
This review provides a comprehensive overview of ASMD, focusing on the recent advancements in the understanding of the disease pathophysiology, the variability of clinical manifestations, the need to increase clinician awareness to promote early diagnosis, the evolution of the diagnostic approaches, and current and experimental treatment options.
To cite this article
Acid sphingomyelinase deficiency: a complex and rare disorder that needs clinicians’ awareness
JIM 2024;
1 (4): e634
DOI: 10.61012_202411_634
Publication History
Submission date: 08 Oct 2024
Revised on: 11 Nov 2024
Accepted on: 26 Nov 2024
Published online: 29 Nov 2024