Facts
Why GLA Gene Mutations Matter in Fabry Disease
Fabry disease is caused by mutations in the galactosidase alpha gene (GLA )1,2
There are more than 1000 known mutations of the GLA gene. No single genotypic anomaly causes Fabry disease.3 Instead, a variety of mutations in the GLA gene can give rise to Fabry disease, such as4:
- Missense mutations5
- Compose ~60% of the GLA gene mutations
known to cause Fabry disease - Cause the introduction of an incorrect amino acid
into a protein through a mutation of a single nucleotide
- Compose ~60% of the GLA gene mutations
- Splicing mutations
- Small deletions and insertions
- Large deletions
GLA gene mutations can cause either the absence or the deficiency of functional alpha-Gal A.3,4 In terms of absence, this means that alpha-Gal A is not present, or results in the production of a nonfunctional enzyme.3,4 When functionality is affected, this results in improper protein folding or reduces the stability of alpha-Gal A, often leading to enzyme degradation in the endoplasmic reticulum prior to normal transport to the lysosome.4
