Fabry Disease (GLA)
Fabry disease is a lysosomal storage disorder due to deficiency in the lysosomal enzyme glycohydrolase alpha-galactosidase A (α-GAL A) (Brady et al., N Engl J Med. 1967; 276: 1163-1167). The enzymatic deficiency results in the progressive accumulation of globotriaosylceramide and related glycosphingolipids in the vascular endothelium, causing disease manifestations. Fabry Disease is inherited as an X-linked recessive trait, and female carriers may develop the disease. It is a clinically heterogeneous disease even among affected members of the same family (Banikazemi et al., JIMD. 2012; 35(2): 227-243). In male patients with Fabry Disease, two forms are recognized: classic and atypical forms. The classic form is characterized by onset during the first two decades of life and features including corneal and lenticular opacities, angiokeratoma (skin lesions), acroparesthesias (excruciating pain in the extremities) and hypohidrosis (decreased ability to sweat). In the atypical form, symptoms begin later in life and include left ventricular hypertrophy, arrhythmias and /or cardiomyopathy. The classical features are not present in cases with the atypical form of the disease. In female heterozygotes, clinical manifestations are largely determined by random X inactivation (Dobrovolny et al., J Mol Med. 2005; 83: 647-654). Female heterozygotes may be asymptomatic throughout a normal life span or affected with variable severity. Fabry Disease occurs in diverse ethnic groups throughout the world, with an estimate incidence of 1 in 60,000 males (Meikle et al., JAMA. 1999; 281: 249-254). In untreated patients, death results from renal failure, heart failure and/or myocardial infarction.
Both affected males and carrier females are at high risk for cardiac, cerebrovascular and neurologic complications that can benefit from Enzyme Replacement Therapy (ERT), medication, and a screening program (Mehta et al., GeneReviews. 2002; ncbi.nlm.nih.gov/books/NBK1292).
Studies show a 50% reduction in plasma GL-3 (glycosyl ceramide) concentration, improvement in cardiac conduction and renal function, and a decrease of neuropathic pain for patients treated with ERT (Schiffmann et al., Journal of the American Medical Association (JAMA). 2001; 285(21): 2743-2749). ERT has also been proven to stabilize hearing loss, and improve peripheral nerve function and sweating. The risk of major clinical events occurring (death, myocardial infarction, stroke, etc.) decreased by 53% in treated patients. ERT has shown to stabilize deteriorating renal and cardiac function making early diagnosis crucial in maintaining normal function. (Eng et al., Genetics in Medicine. 2006; 8: 539-598). Overall, this safe, well tolerated medication proved to improve the overall quality of life to those treated (Beck et al., European Journal of Clinical Investigation. 2004; 34(12): 838-844).
To treat complications due to renal disease as well as minimize proternuria and albuminemia, ACE/ARB inhibitors should be used (Breunig et al., Kidney International. 2006; 69: 1216-1221). Studies on these angiotensin-converting enzyme inhibitors, when used with ERT's, have shown effective slowing of deterioration of renal function making early diagnosis crucial (Feriozzi et al., American Journal of Nephrology. 2009; 29(5): 353-361).
Since several complications can arise from Fabry Disease, screening with routine renal studies, cardiology exams, and hearing exams is essential to diagnose the progression of Fabry Disease. (Mehta et al., GeneReviews. 2002; ncbi.nlm.nih.gov/books/NBK1292).
For more information on GLA testing, please see our full Test Description.
This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.