AUTHOR=Molnar Maria Judit , Szlepak Tamas , Csürke Ildikó , Loth Szendile , Káposzta Rita , Erdős Melinda , Dezsőfi Antal 

TITLE=Case report: The spectrum of SMPD1 pathogenic variants in Hungary

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1158108

DOI=10.3389/fgene.2023.1158108

ISSN=1664-8021

ABSTRACT=<p>Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease caused by biallelic pathogenic variants in the sphingomyelin phosphodiesterase-1 (<italic>SMPD1</italic>) gene. Acid sphingomyelinase deficiency is characterized by a spectrum of disease and is broadly divided into three types (ASMD type A, ASMD type A/B, and ASMD type B). More than 220 disease-associated <italic>SMPD1</italic> variants have been reported, and genotype/phenotype correlations are limited. Here we report the first description of all six diagnosed acid sphingomyelinase deficiency cases in Hungary. Nine <italic>SMPD1</italic> variants are present in this cohort, including 3 <italic>SMPD1</italic> variants (G247D, M384R, and F572L), which have only been described in Hungarian patients. All described variants are deemed to be pathogenic. Eight of the variants are missense, and one is a frameshift variant. The treatment of an ASMD type A/B patient in this cohort using hematopoietic stem cell transplantation is also detailed. This study may help to support diagnosis, patient genetic counseling, and management of acid sphingomyelinase deficiency.</p>