Basic genetics of Fabry’s disease which can cause cardiomyopathy

Fabry’s disease is a lysosomal storage disease. Cardiovascular manifestations could be left ventricular hypertrophy, myocardial fibrosis, heart failure and arrhythmias [1]. The genetic transmission has been called X-linked rather than X-linked recessive which we are more familiar with disorders like hemophilia. GLA gene needed for the production of alpha-galactosidase A is defective in Fabry’s disease. GLA gene is located on X chromosome. Manifestations of GLA mutations are more severe in men who are hemizygous for the gene while it is less severe in women who are heterozygous as they have one normal gene and an abnormal gene. That is the reason for calling it as X-linked disease than a typical X-linked recessive disorder. The disease manifests later in those females. Reduced α-galactosidase A activity leads to accumulation of globotriasylceramide (Gb3) in lysosomes of affected tissues, including the heart. Now it is possible to treat Fabry’s disease with enzyme replacement. But early diagnosis and treatment are needed to slow progression of disease and prevent major cardiac complications.

References

1. Pieroni M, Moon JC, Arbustini E, Barriales-Villa R, Camporeale A, Vujkovac AC, Elliott PM, Hagege A, Kuusisto J, Linhart A, Nordbeck P, Olivotto I, Pietilä-Effati P, Namdar M. Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2021 Feb 23;77(7):922-936. doi: 10.1016/j.jacc.2020.12.024. PMID: 33602475.