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

TL;DR

A new GLA gene variant was found in an asymptomatic woman, but it was determined not to cause Fabry disease.

Contribution

The study confirms the benign nature of the p.Met70Val GLA variant through comprehensive clinical evaluation.

Findings

The p.Met70Val GLA variant was not associated with significant organ involvement.

The variant was confirmed to be benign in the asymptomatic patient.

Comprehensive evaluation is crucial for determining the pathogenicity of new GLA variants.

Abstract

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.

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.

The analysis revealed that there were no signs of significant organ involvement, and the benignity of the variant was confirmed.

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.

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