ASMD

GENETIC PROFILE

ASMD is an autosomal recessive LSD caused by pathogenic variants in the ASM enzyme–encoding gene sphingomyelin phosphodiesterase 1 (SMPD1).

Sphingomyelin helps regulate cellular processes, such as cell cycle regulation, cell signaling, and apoptosis.

When ASM activity is deficient, sphingomyelin cannot be sufficiently metabolized; it accumulates in lysosomes, particularly in macrophages and hepatocytes. This accumulation damages cells in multiple organs, leading to potentially life-threatening complications.

Males and females have an equal chance of being affected⁴

Type A Historically known as Niemann-Pick disease type A (NPA) or infantile neurovisceral ASMD
Onset: Early Infancy Phenotype: Rapidly progressive with acute multiorgan manifestations and neurodegeneration Life Expectancy: 2 to 3 years of age

Type A/B Historically known as Niemann- Pick disease type A/B (NPA/B) or chronic neurovisceral ASMD
Onset: Infancy to childhood Phenotype: Variably progressive with multiorgan manifestations and differing degrees of neurologic involvement Life Expectancy: Between early childhood and adulthood

Type B Historically known as Niemann- Pick disease type B (NPB) or chronic visceral ASMD
Onset: Infancy to childhood Phenotype: Chronic with multiorgan manifestations and no or only minor neurologic involvement Life Expectancy: Between childhood and late adulthood

IMPORTANCE OF EARLY DIAGNOSIS

The rarity of ASMD, heterogeneity of its manifestations, and challenging differential diagnosis can result in delayed diagnosis and management of patients.

Early diagnosis of ASMD is critical for appropriate management.

Identifying known disease-causing alleles of ASMD allows for

Individual genetic counseling
Carrier screening for at-risk individuals
Family planning

HOW TO DIAGNOSE

A simple enzyme activity test can be performed on a DBS (dried blood spot) to indicate reduced ASM activity.
A positive DBS enzyme assay is highly indicative of ASMD, but an analysis from a whole blood sample and/or genetic testing is required to confirm the diagnosis.⁵

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