Fabry's disease overview
|
Fabry's disease Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Fabry's disease overview On the Web |
|
American Roentgen Ray Society Images of Fabry's disease overview |
|
Risk calculators and risk factors for Fabry's disease overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sukaina Furniturewala, MBBS[2]
Overview
- Fabry disease (also known as alpha-galactosidase A deficiency, ceramide trihexosidase deficiency, angiokeratoma corporis diffusum, Anderson Fabry disease) is an X-linked recessive inherited lysosomal storage disorder.
- X linked inherited disorders are transmitted
- It occurs as a result of the body's inability to make the enzyme alpha-galactosidase A. This enzyme encoded by the GLA gene located on the long arm of the X chromosome (q21-22) is in-turn responsible for breaking down a type of fat called globotriaosylceramide (Gb3 or GL-3) into building blocks that are used by the cells of the body.
- The Glycosphingolipid storage initiates a cascade of events that begins with the dysfunction of basic metabolic processes on the cellular level followed by progression to cell death, inflammatory events, and progressive major organ dysfunction.[2]
- Three main organ systems commonly affected include the brain, heart and kidney.
- Prenatal and neonatal studies of the histopathology of Fabry disease have confirmed that pathogenic GL3 accumulations occur in the maternal region of the placenta, fetal tissues, and the fetal placenta regions of affected males. In male fetuses affected these accumulations have been found in renal, myenteric plexus, and liver cells.This prenatal storage suggests that the process of Fabry disease may lead to early childhood symptoms[3][4]
- Fabry disease is a rare condition that can affect people regardless of their ethnic background. The prevalence for Fabry's disease is estimated to range from 0.27 to 1.69 per 100,000 in men, and 0.33 to 3.47 per 100,000 in women.
- The disorder is termed X linked as the mutated gene is located only on the X chromosome. In males (who have only one X chromosome), one altered copy of the GLA gene is sufficient to cause the condition however since females have two copies of the X chromosome, one altered copy of the gene in the cells usually leads to less severe symptoms in females than in males and in some cases none at all.
- The significance of Fabry's disease stems from data that suggests significant medical problems in many females who have only one altered copy of the GLA gene unlike other X linked diseases that generally have most women carriers remaining asymptomatic. The women carrying this mutation only on one X chromosome can experience many of the classic features of the disorder, including nervous system abnormalities, kidney failure and heart disease. Other possible symptoms reported include high blood pressure, chronic pain and fatigue.
- A small percentage of females who carry a mutation in one copy of the GLA gene never develop signs and symptoms of Fabry disease.[5]
References
[2] Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006;8: 539–548.
[3] Elleder M, Poupĕtová H, Kozich V . Fetal pathology in Fabry’s disease and mucopolysaccharidosis type I. Cesk Patol 1998;34:7–12.
[4] Thurberg BL, Politei JM . Histologic abnormalities of placental tissues in Fabry disease: a case report and review of the literature. Hum Pathol 2012;43:610–614.
[5] Deegan PB, Baehner AF, Barba Romero MA, Hughes DA, Kampmann C, Beck M; European FOS Investigators. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet. 2006 Apr;43(4):347-52. Epub 2005 Oct 14. Citation on PubMed or Free article on PubMed Central