• Fabry disease
• α-galactosidase deficiency
• GLA deficiency
• X inactivation

Anderson-Fabry disease (E C 3.2.1.22, MIM 301500) is an X linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (GLA).^1,2 The onset of the disease and the severity of clinical manifestations depend principally on residual GLA enzymatic activity.¹ Fabry disease can be classified into two clinical phenotypes: the classical form and the cardiac variant.^1,3 The classical form is mainly characterised, in affected hemizygous males, by angiokeratoma, acroparaesthesias, hypohidrosis, pains, fever crises, and involvement of the kidneys, brain, and heart. Neurological and/or psychological manifestations with personality disturbances can also occur.¹ The cardiac variant is characterised by symptoms restricted to cardiac abnormalities, including conduction defects and/or late onset cardiomyopathy with left ventricular hypertrophy.^1,3,4 A prevalence of Fabry disease in a referral population of male patients with a clinical diagnosis of late onset hypertrophic cardiomyopathy (HCM) has also been reported.⁵ The X linked disorders affect males, while the female carriers are generally asymptomatic, owing in part to the random inactivation of the X chromosome.⁶ Fabry female carriers can be asymptomatic or clinically affected, usually with a late onset and mild form of the disease. Corneal abnormalities are the most frequent clinical manifestations.¹

The human GLA gene, mapped on Xq22, is organised in seven exons encompassing over 12 kb.⁷ So far, about 265 mutations spread throughout the GLA gene in all exons have been reported in the Human Gene Mutation Database Web site and, in addition, a further 65 have been published.^8,9