Anderson-Fabry Disease (AFD): A Rare Genetic Disorder with Multi-System Affects

Anderson-Fabry Disease (AFD) is the second most common of lipid storage diseases affecting approximately 1 in 100,000 people. The mutation occurs in the alpha-galactosidase A (GLA) gene. Because of the X-chromosome location of GLA, the disorder affects males more frequently than females. Males do not pass AFD on to any male offspring but the mutation is passed to all daughters. In turn, females have a 50% chance of passing the disease to either sex with each pregnancy. No specific ethnicity has been associated with AFD.

AFD causes an absence or extremely deficient activity of the enzyme, alpha-galactosidase A (α-Gal A). GLA is responsible for instructing cells to make α-Gal A, which in turn performs lysosomal actions. Lysosomes are a key component in the break down and digestion of complex glycolipids. The result of absent lysosomes is a continuous build-up of glycolipids which leads to multi-system organ affects with particular damage to arteries, the autonomic nervous system, the heart and of course, the kidneys.

True neuropathic pain called acroparasthesia develops, which in turn causes disability for those afflicted. This extreme pain can be brought on by exertional means, such as exercise or with changes in weather, such as extreme cold or heat. Angiokeratomas: a disseminated, fine grain appearing flat rash may appear and is unique to AFD. The gut is affected causing a myriad of gastrointestinal symptoms. The lymphatic system becomes impaired leading to the development of hypohidrosis. Corneal opacities and clouding can be seen on ophthalmic examination but usually does not impair vision. As the disease progresses, left ventricular hypertrophy and cardiomyopathy are typical findings. Strokes and transient ischemic attack occur. As for the renal system, progressive proteinuria, renal insufficiency and ultimately renal failure is likely to occur.

Prior to enzyme replacement therapy (ERT) and transplant or dialysis renal replacement therapies, mortality was high. As an example, in 1967, the average age of death for affected males was about 40 years. Current treatment typically includes adjunctive therapies and embody a multi-disciplinary approach. Genetic and diagnostic testing that includes newborn screening have been increasing recently, as well.

If you would like to learn more about rare genetic diseases and how they are treated, please visit the National Organization for Rare Disorders Rare Disease Database and be sure to engage your local nephrology team.