ASMD Testing

What is Acid Sphingomyelinase Deficiency (ASMD or Niemann-Pick A/B)?

Acid sphingomyelinase deficiency (ASMD, historically classified as a Niemann-Pick disease type A, type B, and type A/B), is a rare lysosomal storage disease and autosomal recessive genetic disorder with extensive phenotypic heterogeneity.1 It results from genetic mutations that lead to acid sphingomyelinase (ASM) enzyme activity insufficiency and a subsequent abnormal accumulation of the primary ASM substrate and other related lipids in cells of the monocyte‑macrophage system.1

Mutations in the ASM-encoding gene, SMPD1 (sphingomyelin phosphodiesterase 1), are the cause of ASMD.1 The deficiency of ASM and subsequent accumulation of sphingomyelin and metabolically-related lipids in cells results in a foam-like cell appearance.1 This build-up of cellular substrate in ASMD causes progressive cell and tissue damage and impairs the functioning of multiple organs. ASMD ranges from rapidly progressing severe neurovisceral forms to chronic neurovisceral and chronic visceral forms.1,2

Both Gaucher disease and ASMD may present with similar clinical features, including thrombocytopenia and splenomegaly,3 and have a wide phenotypic spectrum with neurological and visceral manifestations.1,4 ASMD also has an intermediate chronic neurovisceral form.2 However, there are differences between ASMD and Gaucher diseases. For example, pulmonary involvement (interstitial lung disease) and respiratory infections are more commonly associated with ASMD, whereas anemia is more common with Gaucher disease than ASMD.3

What is the Incidence of ASMD?

ASMD incidence is estimated at approximately 0.5 per 100,000 births.1

The Roadmap2Rare Diagnostic Program Eligibility

This rare disease testing program is designed for HCPs with eligible patients when there is clinical suspicion of ASMD. The program includes single disorder testing for ASMD (ASM enzyme assay with reflex to SMPD1 sequencing if deficient). ASMD testing is also performed in parallel with Gaucher testing requested through the program.

*Note: this diagnostic program is not appropriate for carrier testing.

What is the ASMD Test?

For single disorder testing, the algorithm is as follows:

  1. ASM enzyme is assayed
  2. If enzyme levels are found to be deficient, SMPD1 sequencing is performed

In the event that sequencing or enzyme assay activity testing has been performed previously, individual tests can be ordered.


  1. McGovern MM, et al. Orphanet J Rare Dis. 2017;12(1):41.
  2. McGovern MM, et al. Genet Med. 2017;19(9):967–974.
  3. Cappellini MD, et al. Eur J Intern Med. 2023:108:81–84.
  4. Baris HN, et al. Pediatr Endocrinol Rev. 2014;12:72–81.

The Roadmap2Rare Diagnostic Program is not intended to and should not interfere in any way with a clinician’s or patient’s independent judgment and freedom of choice in the testing and treatment options for these diseases. Clinicians and patients should always consider the full range of testing and treatment options and select those most appropriate for the individual patient. The identifying information of patients and clinicians is not shared with Sanofi Canada.