Acid sphingomyelinase deficiency (ASMD), commonly called Niemann-Pick A/B disease, is an autosomal recessively inherited lysosomal storage disorder resulting from a deficiency in acid sphingomyelinase (ASM) activity [1]. The incidence of this illness is 1 in 250,000 to 400,000 births depending on the subtype. This rare disorder, belonging to sphingolipidoses, is caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1). ASM deficiency results in the accumulation of the primary ASM substrate, sphingomyelin, and other metabolically related lipids mainly in cells of the monocyte macrophage system in the spleen and lung as well as in hepatocytes.

These substrates can build up over time, causing progressive cell and tissue damage and functional impairment of multiple organs [2]. The clinical manifestation of sphingolipidosis leads often to misclassification between acid sphingomyelinase deficiency (ASMD) and Gaucher disease (See figure 1).

Key Symptoms
Type B
Type 1
Abnormal Pulmonary Function
Figure 1: Example of shared symptoms of ASMD and Gaucher disease.

In a recent publication, our research group investigated a cohort of 31,838 individuals suspected to have Gaucher disease from 61 countries between 2017 and 2022.

One in four cases suspected for Gaucher disease was actually affected with ASMD

For all samples, both Acid-β-glucocerebrosidase and acid sphingomyelinase enzyme activities were measured in dried blood spot specimens by tandem mass spectrometry followed by genetic confirmatory testing in potential positive cases. In total, 5933 symptomatic cases showed decreased enzyme activities and were submitted for genetic confirmatory testing. This study reveals that one in four cases suspected of Gaucher disease was actually affected with ASMD. This emphasizes the importance of a diagnostic strategy using differential biochemical testing including genetic confirmatory testing in clinically suspected cases of sphingolipidoses.

You can read the full article in Molecular Genetics and Metabolism.

[1] E.H. Schuchman, R.J. DesnickTypes A and B Niemann-Pick diseaseMol. Genet. Metab., 120 (2017), pp. 27-33, 10.1016/j.ymgme.2016.12.008
[2] M.M. McGovern, R. Avetisyan, B.-J. Sanson, O. LidoveDisease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)Orphanet J. Rare Dis., 12 (2017), p. 41, 10.1186/s13023-017-0572-x