Bernstein_2025_Mol.Genet.Metab_146_109233

PURPOSE: This study was designed to more accurately estimate the prevalence of severe, infantile onset, rapidly progressive lysosomal acid lipase deficiency (LALD), an autosomal recessive disorder caused by the homoallelic LIPA gene variant, c.260G>T; p.G87V in patients of Mizrahi Jewish ancestry. The previous estimates of LALD prevalence in Middle Eastern and Mizrahi Jewish populations, ranging from 1 in 12,100 to 1 in 4200, were based on historic, observational case reports and a population genetic screening of 165 Middle Eastern individuals and 162 Mizrahi Jews living in Southern California. METHODS: Carrier screening of 549 Mizrahi Jewish individuals for the c.260G>T; p.G87V LIPA variant and the common, c.894G>A; p.E8SJM(-1)LIPA variant, was carried out to determine their allele frequencies and expected prevalence of LALD in a larger Mizrahi population. RESULTS: This larger population screening study revealed a LIPA p.G87V Mizrahi founder variant allele frequency of 1 in 52.2, conferring a carrier frequency of 1 in 26.1. Therefore, the occurrence of infantile LALD was estimated to be one in 2724.8 Mizrahi Jewish conceptions in Southern California. CONCLUSION: The present, larger study found the prevalence of rapidly progressive, infantile LALD disease was -35 % greater than the previous prevalence estimate in the major U.S. Mizrahi Jewish population.