# 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.

## Key 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.