Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)

Abstract

Background Acid Sphingomyelinase Deficiency (ASMD) is a rare autosomal recessive disorder caused by mutations in the SMPD1 gene. This rarity contributes to misdiagnosis, delayed diagnosis and barriers to good care. There are no published national or international consensus guidelines for the diagnosis and management of patients with ASMD. For these reasons, we have developed clinical guidelines that defines standard of care for ASMD patients. Methods The information contained in these guidelines was obtained through a systematic literature review and the experiences of the authors in their care of patients with ASMD. We adopted the Appraisal of Guidelines for Research and Evaluation (AGREE II) system as method of choice for the guideline development process. Results The clinical spectrum of ASMD, although a continuum, varies substantially with subtypes ranging from a fatal infantile neurovisceral disorder to an adult-onset chronic visceral disease. We produced 39 conclusive statements and scored them according to level of evidence, strengths of recommendations and expert opinions. In addition, these guidelines have identified knowledge gaps that must be filled by future research. Conclusion These guidelines can inform care providers, care funders, patients and their carers about best clinical practice and leads to a step change in the quality of care for patients with ASMD with or without enzyme replacement therapy (ERT).

Case report: Clinical, imaging, and genetic characteristics of type B niemann pick disease combined with segawa syndrome diagnosed via dual gene sequencing

“…Enzyme replacement therapy (ERT) reduces sphingomyelin accumulation in the lungs, liver, spleen, and other non-central nervous system (CNS) organs and clinical trials have largely proved its efficacy on non-CNS manifestations. Indeed, it is not suitable for treating ASMD CNS involvement since the enzyme do not cross the blood brain barrier (Geberhiwot et al, 2023). ERT has been approved by the Food and Drug Administration (FAD), and the European Medical Agency (EMA).…”

“…Niemann-Pick A/B, also known as acid sphingomyelinase deficiency (ASMD), is a rare autosomal recessive lysosomal storage caused by mutations in the SMPD1 gene encoding the acid sphingomyelinase enzyme (Ota et al, 2020). Based on the clinical phenotype, ASMD has been divided into infantile neurovisceral Niemann-Pick A (NPA), chronic neurovisceral Niemann-Pick A/B (NPA/B), and chronic visceral Niemann-Pick B (NPB) (Geberhiwot et al, 2023). Owing to insufficient acid sphingomyelinase (ASM) activity, excessive accumulation of sphingomyelin in monocytes, macrophages, and tissues leads to clinical symptoms in NPA and NPB.…”

Diagnostic odyssey for patients with acid sphingomyelinase deficiency (ASMD): Exploring the potential indicators of diagnosis using quantitative and qualitative data

“…Finally, ASMD type A/B falls in the middle of the spectrum, with patients experiencing neurodegeneration that develops from infancy to childhood, but is slower in progression than seen in patients with type A [ 3 , 9 ]. There is no clear diagnostic test to distinguish between the subtypes of ASMD in routine clinical use, with clinical presentation typically determining subtype [ 3 , 17 ].…”

ASM Variants in the Spotlight: A Structure-Based Atlas for Unraveling Pathogenic Mechanisms in Lysosomal Acid Sphingomyelinase

“…ASM deficiency leads to acid sphingomyelinase deficiency (ASMD), a rare genetic disorder 12,13 . ASMD results in the accumulation of sphingomyelin and other molecules in various tissues, with varying levels of severity.…”

“…ASMD is primarily caused by mutations in the SMPD1 gene, inherited in an autosomal recessive manner. Common challenges in managing ASMD include misdiagnosis and delayed care due to the paucity of consensus clinical guidelines 12 .…”