DefinePK

Abstract

Fabry disease (OMIM #301500) is a rare X-linked lysosomal storage disease. Generally, lysosomal storagedisease is identified by inappropriate lipid storage in lysosomes due to specific enzyme deficiencies. In case ofFabry disease, the defective enzyme is Alpha-Galactosidase A (Enzyme Commission No- 3.2.1.22). Alpha-Galactosidase A enzyme is involved in the hydrolysis of terminal, non-reducing Alpha-D-galactose residues inAlpha-D-galactosides, including galactose oligosaccharides, galactomannans, and galacto-lipids. The defect inthe enzyme is usually due to pathogenic variants in the GLA gene, present on Human X chromosome(chrX:101397803-101407925, hg38). A mutation in the Alpha-Galactosidase A gene results in the accumulationof globotriaosylceramide and its derivatives throughout lysosomes in the body. A pathogenic, hemizygousAlpha-Galactosidase A variant identified through genetic testing usually confirms the diagnosis in malepatients. In contrast, the presence of a heterozygous pathogenic variant may establish the diagnosis in femalepatients, as heterozygous females may be as severely affected as males or asymptomatic throughout a normallife span. To our knowledge, Fabry disease has not been reported from Pakistan. We report the first case ofFabry disease in a 13-year-old boy presenting with bilateral lower limb acroparesthesia and anhidrosis fromPakistan. At present, he does not have any additional symptoms, including cardiac and renal. Genetic testingthrough targeted panel sequencing revealed a novel pathogenic hemizygous mutation in the Alpha-Galactosidase A gene (c.779G>A, p.Gly260Glu) in this male patient. This variant is present in exon 5 of theAlpha-Galactosidase A gene, which comprises of 429 amino acids. We advised Injection Agalsidase beta, 1mg/kg, I/V infusion every 2 weeks, which is a lifelong enzyme replacement therapy.
How to cite this: Malick AA, Hasan MJ, Ahmad A. A Novel Mutation in The GLA Gene Leading to Fabry Disease - A Case Report from Islamabad, Pakistan. Life and Science. 2025; 6(3): 419-423. doi: http://doi.org/10.37185/LnS.1.1.913