Fabry disease is an X-linked inherited disorder. The defective gene is on the X-chromosome, which is one of the two chromosomes that determine an individual’s sex. Females have two X-chromosomes, one inherited from each parent. Males have one X-chromosome inherited from their mother and one Y-chromosome inherited from their father. (This is why there is no male to male transmission with an X-linked disorder) A female with Fabry disease receives one X-chromosome with a defective gene and one X-chromosome with the normal gene, and thus may have some protection from the major manifestations of the disease. There is less variability with males with Fabry disease, because they only receive one X and it is an abnormal X-chromosome that contains the abnormal gene, they express the disease more severely.

Each male and female child of an affected female has a 50% chance of inheriting the defective gene from its mother with each pregnancy. If the father is the one carrying the Fabry gene, all daughters will inherit the defective gene, but none of the sons will. With all X-linked disorders, fathers do not transmit the affected gene onto their sons.

Fabry is an X-linked disorder, meaning there is no male to male transmission. Fathers (hemizygotes) pass the defective gene onto all their daughters. Mothers (heterozygotes) have a 50% chance with each pregnancy of passing the defective gene onto their children.

The actual incidence of Fabry disease is not known. For the classically affected male, it is estimated that one in 40,000 will have Fabry disease. However, this number does not include female patients, which the estimated number of affected individuals is higher than previously expected, nor does it include those who have a variant form of the disorder. In general, the severity of symptoms correlates inversely with enzyme activity. Classic male patients typically have less than 1% of normal plasma levels of alpha GAL. Females can vary from 0 to 100% thus the wide degree of variability of symptoms and the variant form can range from 1 to 30% of the normal enzyme level, which typically delays the onset of symptoms. For those individuals with residue enzyme levels, their involvement may be less, making it harder to make a diagnosis.