Allele frequency of pathogenic variants causing acid sphingomyelinase deficiency and Gaucher disease in the general Japanese population

Acid sphingomyelinase deficiency (ASMD) and Gaucher disease (GD) are lysosomal storage disorders associated with hepatosplenomegaly and thrombocytopenia. The incidences of ASMD and GD are known to be particularly high in the Ashkenazi Jewish population. Conversely, the number of reported patients with these diseases has been limited in Asian countries, including Japan. Here, we reviewed the allele frequencies of pathogenic variants causing ASMD and GD in the Japanese population and populations with various ancestry backgrounds using the Japanese Multi-Omics Reference Panel 54KJPN and the Genome Aggregation Database v4.0.0. The estimated carrier frequencies of ASMD- and GD-related variants were 1/180 and 1/154 in Japanese individuals, equivalent to disease occurrence frequencies of 1/128,191 and 1/94,791 individuals, respectively. These frequencies are much higher than previously expected. Our data also suggest that there are more patients with a milder form of ASMD and nonspecific clinical findings who have not yet been diagnosed. Understanding the frequency of uncommon genetic disorders like Gaucher disease and acid sphingomyelinase deficiency is important, especially in areas where data is limited. In Japan, the actual number of these diseases is still unknown despite medical progress. Researchers focused on identifying harmful variants of the SMPD1 and GBA1 genes, which are associated with acid sphingomyelinase deficiency and Gaucher disease. This review uses existing genetic data from 54,302 Japanese people and compares it with global data to estimate disease frequency in Japan. The main findings show a higher-than-expected frequency of acid sphingomyelinase deficiency and Gaucher disease in Japan, suggesting that many patients may not be diagnosed due to the rarity and nonspecific symptoms of these diseases. Researchers conclude that their work could increase disease awareness and diagnosis, potentially leading to better treatment results for affected individuals.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.