Inheritance of Fabry Disease

As an X-linked disease, the genetic defect that causes Fabry disease can be transmitted by both males and females. More than 849 gene mutations in the GLA gene for Fabry disease have been  reported. http://fabry-database.org/, last accessed on Oct. 10, 2017
http://www.hgmd.cf.ac.uk/ac/index.php, last accessed on Oct. 10, 2017
 The known  mutations, can be classified under classic Fabry disease, non-classic Fabry disease, benign polymorphisms or pseudo deficiencies. Most of the mutations are still unclassified and too little information is known on natural history to draw a conclusion. There is a wide phenotypic variability seen in age of onset, rate of progression, organ involvement and severity.

As shown in both figures, men with a mutation on the GLA gene will pass this to all their daughters but not to their sons. Females with a mutation on the GLA gene, with each conception, have a 50% chance of passing the defective gene on to all offspring.

Inheritance of GLA mutation (father)

Males with the defective gene transmit it to all of their daughters and none of their sons.

* Affected father to be described as hemizygote with defective gene/mutation and affected females as heterozygote with defective gene

Inheritance of GLA mutation (mother)

Females with the defective gene have a 50% chance of passing it during each pregnancy.

* Affected father to be described as hemizygote with defective gene/mutation and affected females as heterozygote with defective gene

However, although a positive family history is a strong indicator for Fabry disease, de novo or spontaneous mutations have been documented. Redonnet-Vernhet I, et al. Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the α-galactosidase A gene. J Med Genet 1996;33:682–88.<br /> Hasholt L, et al. A Fabry's disease heterozygote with a new mutation: biochemical, ultrastructural, and clinical investigations. J Med Genet 1990;27:303–306.  Thus, absence of a family history does not rule out a diagnosis of Fabry disease.