Understanding Fabry Disease
Fabry disease is caused by a defect in the GLA gene. The faulty GLA gene results in a deficiency of the enzyme alpha-galactosidase A, more commonly referred to as α-Gal A. The lysosomal enzyme, α-Gal A, is an essential enzyme required to breakdown globotriaosylceramide (also known as Gb3 or GL-3). In people living with Fabry disease, Gb3 accumulates in various cells throughout the body causing the progressive clinical signs and symptoms of the disease.1
Classic Fabry disease signs and symptoms begin in early childhood or adolescence with the appearance of hallmark red, raised lesions on the skin (angiokeratomas), episodic crises of severe pain in the hands and feet (acroparesthesias), alternating diarrhea and constipation, difficulty sweating (hypohidrosis or anhidrosis) and corneal opacities. Although protein in the urine (proteinuria) may be an early sign of Fabry disease, kidney problems usually occur in the third to fifth decade of life.2 As Fabry disease progresses, irreversible organ damage can result in potentially life-threatening kidney damage, cardiac disease and early stroke.2 Many of the symptoms of Fabry disease are common in the general population, often delaying the diagnosis.
How is Fabry Disease Inherited?
Fabry disease is a genetic disease that is passed down through an X-linked inheritance pattern. Females inherit an X chromosome from both parents. Males inherit an X chromosome from their mother and a Y chromosome from their father. Therefore, sons of affected males cannot inherit the disorder, or said another way, there is no father-to-son transmission. All daughters of an affected male will inherit the affected X chromosome.
If the mother is affected with Fabry disease, she has a 50/50 chance with each pregnancy of passing on the faulty gene to her children. Thus, each son has a 50 percent chance of inheriting Fabry disease and each daughter has a 50% chance of carrying one copy of the defective gene.4
Females that carry one faulty gene can be affected with Fabry disease. Fabry disease runs in families. If one person in the family is affected, chances are additional family members may also be affected.5 A genetic counselor can help determine who in the family is at risk for Fabry disease.
How Common is Fabry Disease?
Fabry disease is considered a rare genetic disorder with an estimated incidence of approximately one in 40,000 males and one in 118,000 females.6 Newborn screening studies being conducted around the world may help shed light on the true incidence of Fabry disease.7
The following links provide additional patient-friendly information on Fabry disease:
1 Garman SC et al. The Molecular Defect Leading to Fabry Disease: Structure of Human α-Galactosidase.
Journal of Molecular Biology. Volume 337, Issue 2: 319-335 (2004).
2 Germain DP. Fabry Disease.
3 Linhart A et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey.
Eur Heart J. 28:1228–35 (2007).
4 Genetics Home Reference Help Me Understand Genetics, Inheriting Genetic Conditions (2017).
https://ghr.nlm.nih.gov. Accessed August 2017.
5 Laney et al. Diagnosis of Fabry disease via analysis of family history.
Journal of Genetic Counseling, 17(1), 79-83 (2008).
6 Meikle, PJ, et al., Prevalence of Lysosomal Storage Disorders. JAMA 1999; 281(3):249-254; and Desnick, RJ, Enzyme Replacement and Beyond. J Inherit Metab Dis (2001) 24: 251.
7 Lin HY et al. High incidence of the cardiac variant of Fabry disease revealed by newborn screening in the Taiwan Chinese population.
Circ Cardiovasc Genet.2:450–6 (2009).