About ASMD

Understanding ASMD:
A progressive, often life-threatening genetic disease1

Multiorgan impact and diagnostic delays can have severe health consequences2

ASMD (acid sphingomyelinase deficiency) is a genetic disease with progressive and multisystemic symptoms that can lead to early mortality. The disease is caused by deficiency of the enzyme acid sphingomyelinase (ASM), resulting in buildup of the substrate sphingomyelin in cells. Accumulation of sphingomyelin impacts major organs, which may include the liver, lungs, spleen, and the hematologic and gastrointestinal systems.1

*Based on a prospective, cross-sectional survey of 59 ASMD type B patients

ASMD is a spectrum of disease, with 3 types that vary in age of onset, rate of progression, and impact on lifespan.1,2,4

TYPE A
TYPE A/B
TYPE B (most common)
Onset Early infancy Infancy to childhood Infancy to adulthood
Phenotype Rapidly progressive, severe multiorgan involvement and neurodegeneration Slower progressive, variable multiorgan disease and neurodegeneration Slower progressive, variable multiorgan disease with little to no neurological involvement
Life expectancy 2 to 3 years of age Childhood to mid-adulthood Childhood to late adulthood

Based on patient population from a multicenter, historical cohort study (N=100).

ASM enzyme deficiency is the underlying cause of ASMD2

ASMD is caused by pathogenic variants in the SMPD1 gene – which encodes acid sphingomyelinase (ASM) – resulting in ASM enzyme deficiency.2

Cell with normal ASM enzyme activity
Cell with normal ASM enzyme activity
Cell with deficient ASM enzyme activity
Cell with deficient ASM enzyme activity
Normal cell structureCell
LysosomeLysosome
SphingomyelinSphingomyelin
The following video depicts the mechanism of ASMD pathogenesis
Signs and symptoms of ASMD
There are hallmark signs and symptoms of ASMD1
If you suspect ASMD testing is simple
Suspect ASMD? Testing is simple2
References:
  1. McGovern MM, Avetisyan R, Sanson BJ, Lidove O. Orphanet J Rare Dis. 2017;12(1):41.
  2. McGovern MM, Dionisi-Vici C, Giugliani R, et al. Genet Med. 2017;19(9):967-974.
  3. McGovern MM, Wasserstein MP, Giugliani R, et al. Pediatrics. 2008;122(2):e341-e349.
  4. Cox GF, Clarke LA, Giugliani R. Burden of illness in acid sphingomyelinase deficiency: a retrospective chart of 100 patients. JIMD Rep. 2018;41:119-129.
  5. Eyester KM. The membrane and lipids as integral participants in signal transduction: lipid signal transduction for the non-lipid biochemist. Adv Physiol Educ. 2007;31(1):5-16.
  6. Schuchman EH, Desnick R. Types A and B Niemann-Pick disease. Mol Genet Metab. 2017;120(1-2):27-33.