Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD)

Melissa Wasserstein,Carlo Dionisi-Vici,Roberto Giugliani,Wuh-Liang Hwu,Olivier Lidove,Zoltan Lukacs,Eugen Mengel,Pramod K Mistry,Edward H Schuchman,Margaret Mcgovern

doi:10.1016/j.ymgme.2018.11.014

Abstract

BackgroundAcid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, results from mutations in SMPD1, the gene encoding acid sphingomyelinase (ASM). As a result, sphingomyelin accumulates in multiple organs including spleen, liver, lung, bone marrow, lymph nodes, and in the most severe form, in the CNS and peripheral nerves. Clinical manifestations range from rapidly progressive and fatal infantile neurovisceral disease, to less rapidly progressing chronic neurovisceral and visceral forms that are associated with significant morbidity and shorter life span due to respiratory or liver disease. ObjectivesTo provide a contemporary guide of clinical assessments for disease monitoring and symptom management across the spectrum of ASMD phenotypes. MethodsAn international group of ASMD experts in various research and clinical fields used an evidence-informed consensus process to identify optimal assessments, interventions, and lifestyle modifications. ResultsClinical assessment strategies for major organ system involvement, including liver, spleen, cardiovascular, pulmonary, and neurological/developmental are described, as well as symptomatic treatments, interventions, and/or life style modifications that may lessen disease impact. ConclusionsThere is currently no disease-specific treatment for ASMD, although enzyme replacement therapy with a recombinant human ASM (olipudase alfa) is in clinical development. Current monitoring addresses symptoms and multisystem involvement. Recommended interventions and lifestyle modifications are designed to address morbidity and disease complications and improve patient quality of life. While infantile neurovisceral ASMD is uniformly fatal in early childhood, patients with chronic visceral and chronic neurovisceral ASMD require appropriate management throughout childhood and adulthood by an interdisciplinary clinical team.

Highlights

Acid sphingomyelinase deficiency (ASMD), known as Niemann Pick disease type A and type B, is a rare lysosomal storage disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase (ASM) due to bi-allelic mutations in the sphingomyelin phosphodiesterase 1 gene, SMPD1 [1,2]
This review presents global expert opinion consensus on current practices for disease monitoring in patients across the spectrum of ASMD phenotypes
Current monitoring of ASMD is targeted towards reducing the impact of individual symptoms, with treatments, interventions, and lifestyle modifications designed to address morbidity and disease complications and improve patient quality of life

Summary

Introduction

Acid sphingomyelinase deficiency (ASMD), known as Niemann Pick disease type A and type B, is a rare lysosomal storage disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase (ASM) due to bi-allelic mutations in the sphingomyelin phosphodiesterase 1 gene, SMPD1 [1,2]. ASMD results primarily in the progressive accumulation of sphingomyelin within the mononuclear phagocytic system and hepatocytes, and manifests as a multi-system disease involving the spleen, liver, lung, bone marrow, and lymph nodes, and in severe forms of the disease, the CNS and peripheral nervous system. Clinical manifestations range from rapidly progressive and fatal infantile neurovisceral disease, to less rapidly progressing chronic neurovisceral and visceral forms that are associated with significant morbidity and shorter life span due to respiratory or liver disease

Objectives

Methods

Conclusion