Basic Genetic Info

Fabry disease is inherited in a X-linked manner. This refers to the location of the GLA gene (Fabry gene) mutation/defect on the X chromosome. The X and Y chromosomes, two of the 23 pairs of chromosomes in the body, among many other functions, determine the sex of an individual. Females have two X chromosomes. Males have one X chromosome and one Y chromosome.

Fabry affected males pass their X chromosome to all of their daughters. In this way, all daughters of affected males will have the gene for Fabry disease. This is assuming paternity is not of concern.

Affected males do not pass the Fabry disease gene to any of their sons. Sons receive their father’s Y chromosome and cannot inherit Fabry disease from their father.

Every time a female with the Fabry gene has a child, there is a 50% chance that she will pass her affected X chromosome to the child, and a 50% chance that she will pass her normal X chromosome to the child. This means there is a 50% chance that every daughter and every son born to a female with the Fabry gene will inherit the affected X chromosome and have the Fabry gene.

Easy Summary: Fathers pass the Fabry gene to all of their daughters ond none of their sons. Mothers pass the Fabry gene on average half of their children, boys and girls, but it is a random process so a mother could pass the Fabry gene to all of or none of her children or any number in between.

As recently as 2001 it was believed that Fabry disease was a typical X-linked recessive disease in which females are carriers only and could not have symptoms.1 However, researchers and treating physicians have learned that Fabry disease does not have an X-linked “recessive” inheritance pattern and females without Fabry disease symptoms are the exception not the rule.

Some females have symptoms equal to severely affected males with classic Fabry disease, while others may be seemingly asymptomatic, only experience mild symptoms, or exhibit any variation of symptoms in between. A high percentage of females carrying the Fabry disease gene are affected and have significant disease symptoms.

It is generally preferred to refer to a female with a disease causing Fabry mutation but who doesn’t have symptoms as an asymptomatic female rather than a “carrier”. The term “carrier” is usually reserved for a female who is a carrier but CANNOT have symptoms such as in an X-linked recessive disease.

When a gene mutation spontaneously occurs in a family for the first time rather than by inheritance, it is called a de novo mutation.

Reference: 1. Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP: Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 2008, 93:112-128.