No evidence of Fabry disease in a patient with the new p.Met70Val GLA gene variant

• Published in: Molecular genetics & genomic medicine 2024-06, Vol.12 (6), p.e2390-n/a
• Main Authors: Capelli, Irene, Di Costanzo, Roberta, Aiello, Valeria, Lerario, Sarah, De Giovanni, Paola, Montevecchi, Marcello, Cerretani, Davide, Donadio, Vincenzo, La Manna, Gaetano, Mignani, Renzo
• Format: Article
• Language: English
• Subjects: Adult; alpha-Galactosidase - genetics; alpha-Galactosidase - metabolism; Asymptomatic; Biopsy; Clinical Report; Clinical Reports; Enzymatic activity; Enzyme activity; Enzymes; Fabry disease; Fabry Disease - genetics; Fabry Disease - pathology; Fabry's disease; Female; Females; Galactosidase; Genotype & phenotype; Globotriaosylceramide; Glycosphingolipids; Humans; Leukocytes; Lysosomal storage diseases; Males; Pathogenicity; Pathogens; Patients; Pediatrics; Phenotype; Phenotypes; Signs and symptoms; Urine; variant; variant of unknown significant
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2390

Background Fabry disease (FD) is a rare X‐linked lysosomal storage disorder caused by variants in GLA gene leading to deficient α‐galactosidase A enzyme activity. This deficiency leads to the accumulation of glycosphingolipids, particularly globotriaosylceramide (Gb3), in various tissues and organs, which can result in life‐threatening complications. The clinical presentation of the disease can vary from the “classic” phenotype with pediatric onset and multi‐organ involvement to the “later‐onset” phenotype, which presents with predominantly cardiac symptoms. In recent years, advances in screening studies have led to the identification of an increasing number of variants of unknown significance that have not yet been described, and whose pathogenic role remains undetermined. Methods In this clinical report, we describe the case of an asymptomatic adult female who was found to have a new variant of unknown significance, p.Met70Val. Given the unknown pathogenic role of this variant, a thorough analysis of the potential organ involvement was conducted. The clinical data were analyzed retrospectively. Results The analysis revealed that there were no signs of significant organ involvement, and the benignity of the variant was confirmed. Conclusion This case underscores the importance of a comprehensive evaluation of new variants of unknown significance to establish their pathogenicity accurately. In this case report, we describe the case of an asymptomatic adult female who was found to have a new variant of unknown significance, p.Met70Val. Given the unknown pathogenic role of this variant, a thorough analysis of the potential organ involvement was conducted. The analysis revealed that there were no signs of significant organ involvement, and the benignity of the mutation was confirmed. This case underscores the importance of a comprehensive evaluation of new variants of unknown significance to establish their pathogenicity accurately.