Novel Galactosidase-Beta-1 Variant in Infantile GM1 Gangliosidosis: A Case Report

TL;DR

A one-year-old girl with infantile GM1 gangliosidosis was found to have a new GLB1 gene variant, highlighting the importance of genetic testing for early diagnosis.

Contribution

A novel GLB1 variant, c.1525T>A (p.Trp509Arg), is reported and contributes to the mutational spectrum of GM1 gangliosidosis.

Findings

A novel homozygous GLB1 variant was identified in a patient with infantile GM1 gangliosidosis.

The variant is absent from population databases and predicted to be deleterious.

The case highlights the importance of genetic testing in diagnosing and managing GM1 gangliosidosis.

Abstract

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder caused by pathogenic GLB1 variants that impair β-galactosidase activity, resulting in GM1 ganglioside accumulation. The infantile (type I) form is the most severe. We describe the case of a one-year-old girl born to consanguineous parents who presented with developmental regression, hypotonia, coarse facial features, hepatosplenomegaly, macular cherry-red spots, Mongolian spots, and sensorineural hearing loss. Whole-exome sequencing revealed a novel homozygous GLB1 variant, NM_000404.4:c.1525T>A (p.Trp509Arg), absent from population databases and predicted deleterious by in silico tools. According to the American College of Medical Genetics and Genomics guidelines, it is classified as a variant of uncertain significance, though the phenotype-genotype match suggests pathogenicity. This case broadens the GLB1 mutational spectrum and underscores the value of early genetic testing for diagnosis, counseling, and management.

Figures