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to the Fabry Disease Awareness website. The purpose of this site is to raise awareness of Fabry disease amongst healthcare professionals. This site provides a comprehensive introduction to Fabry disease, outlining its aetiology, pathophysiology, associated signs and symptoms, diagnosis and management approaches.
Fabry disease (also known as Anderson–Fabry disease) is a genetic lysosomal storage disorder1 that was first described in 1898 by William Anderson and Johannes Fabry. The disease results from the progressive accumulation of glycosphingolipids, in particular globotriaosylceramide (Gb3), in tissues and organs throughout the body.2,3 This is caused by a deficiency in (or absence of) the enzyme α-galactosidase (α-Gal) A, owing to a mutation in the Xq22 region of the X chromosome, which controls enzyme production.4–7 Deficiency of α-Gal A in Fabry disease leads to accumulating glycolipids in tissues and/or blockage of blood vessels.8,9 Lysosomal accumulation of Gb3 occurs particularly in the kidneys, heart, nervous system and in the vascular intima and media.3,10
The estimated incidence of Fabry disease is 1 in 117 000 live births1,2 and the estimated prevalence is 1 in 40 000–60 000 males3 and 1 in 20 000 females.4 Fabry disease is reported in an estimated 0.5‒1.2%* of young individuals who have had a stroke5,6 and ~1–2% of individuals with hypertrophic cardiomyopathy.7 *A range derived from two prospective multicentre studies
Hypertrophic cardiomyopathy: Hypertrophic cardiomyopathy is defined by the presence of increased left ventricular wall thickness that is not solely explained by abnormal loading conditionsdies
Fabry disease is a sex-linked disease because the α-Gal gene (GLA) is found on the X chromosome.1–5 Over 700 different mutations in the GLA gene can cause Fabry disease.5 The most common mutations are point mutations (missense, 55.9%; nonsense, 11.2%), followed by rearrangements of <60 nucleotides (26.8%).6 Larger rearrangements of bases arise more rarely (1.9%) and involve deletions and duplications.6 Data from patients in the Fabry Outcome Survey (FOS, Shire-sponsored international registry) agree well with these figures.6
Fabry disease has previously been classified as an X-linked, recessive genetic disorder; however, females who carry the Fabry gene may show signs and symptoms of the disease. Fabry disease is therefore now described as ‘following X-linked inheritance’1 and the use of the term ‘carrier’ for females with the Fabry gene may no longer be appropriate.2
Males inherit a mutant GLA gene from their mother only (due to its location on the X chromosome) and are therefore always hemizygous for the Fabry gene. Consequently, males only pass the mutant gene to their daughters.3 Females typically carry a single mutant gene on one of their X chromosomes and are therefore heterozygous for the Fabry gene.
Although it is possible for a female to carry a mutant gene on both X chromosomes, the homozygous form is extremely rare.4 A heterozygous female with the Fabry disease gene has a 50% chance of passing it on to her offspring regardless of their sex.3