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Review
. 2019 Feb;126(2):98-105.
doi: 10.1016/j.ymgme.2018.11.014. Epub 2018 Nov 29.

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

Melissa Wasserstein  1 , Carlo Dionisi-Vici  2 , Roberto Giugliani  3 , Wuh-Liang Hwu  4 , Olivier Lidove  5 , Zoltan Lukacs  6 , Eugen Mengel  7 , Pramod K Mistry  8 , Edward H Schuchman  9 , Margaret McGovern  10
Affiliations
Review

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

Melissa Wasserstein et al. Mol Genet Metab. 2019 Feb.

Abstract

Background: Acid 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.

Objectives: To provide a contemporary guide of clinical assessments for disease monitoring and symptom management across the spectrum of ASMD phenotypes.

Methods: An 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.

Results: Clinical 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.

Conclusions: There 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.

Keywords: ASMD; Acid sphingomyelinase deficiency; Patient monitoring.

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Conflict of interest statement

Disclosures

Sanofi Genzyme provided support, including an honorarium for the authors to meet and discuss the consensus guidelines, in Baltimore, Maryland, October 11, 2015. The authors were not paid an honorarium to author the resulting publication. CD-V has received research grants, investigator fees, speaker honoraria, and reimbursement of travel expenses to attend scientific meetings from Sanofi Genzyme; RG has received investigator fees, consultant and speaker honoraria, and reimbursement of travel expenses to attend scientific meetings from Sanofi Genzyme; W-LH has received research grant and lecture honoraria from Sanofi Genzyme; OL has received travel grants and speaker honoraria from Sanofi Genzyme and Amicus; ZL has received travel grants, honoraria and research grants from Sanofi Genzyme; MM has no conflicts of interest to declare; EM has received investigator fees, speaker honoraria, and reimbursement of travel expenses to attend scientific meetings from Sanofi Genzyme; PKM has received research grants and lecture honoraria from Sanofi Genzyme; ES is an inventor on several patents that have been licensed by Mount Sinai to Sanofi Genzyme for the treatment and diagnosis of ASMD. He is also a consultant to Sanofi Genzyme and receives a research grant for the study of ASMD; MW has received travel grants, honoraria, and investigator fees from Sanofi Genzyme. The opinions represent those of the authors based on their clinical expertise and experience and do not reflect those of Sanofi Genzyme.

References

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