Fabry disease


What is Fabry disease?

Fabry disease is a progressive genetic condition that causes health problems like extreme tiredness (fatigue), little to no sweating, a reddish-purplish skin rash (angiokeratomas), burning pain in the hands and feet, problems in the heat and cold, frequent diarrhea and constipation, and early heart, stroke and kidney disease. Fabry disease happens when a person's body does not make enough of an enzyme called alpha-galactosidase A (alpha-Gal) because they have changes or mutations in the GLA gene. When alpha-gal is not working, a fatty substance called globotriaosylceramide (GL-3 or Gb3) builds up in the body's lysosomes (the "recycling centers" of the cell). Gb3 storage leads to narrowed blood vessels that then cause health problems all over the body, particularly in the skin, kidneys, heart, brain, intestines and nerves.

Fabry disease can be associated with a wide range of severity but it is commonly divided into two types, "classic" and "non-classic or late onset." Both men and women can have classic and non-classic Fabry disease. Because of the way Fabry disease is passed through families, symptoms often vary more in women than in men. The type of Fabry disease often depends on the age symptoms start, the organs affected by the disease, how fast the disease progresses, and how severe symptoms become. Classic Fabry disease symptoms in males and females typically start in the first 3-10 years of life with onset of burning pain in the hands and feet, decreased sweating, problems in the heat, a reddish-purplish rash, and gastrointestinal issues such as diarrhea, bloating, pain and constipation. Without treatment, the classic form of the disease progresses into kidney, heart, and neurologic problems between the ages of 20 to 45. In non-classic Fabry disease, symptoms may start somewhat later in life and may more severely affect one organ like the heart or kidney. It is important to note that in non-classic Fabry disease, heart disease and other symptoms still occur earlier than average men and women, so it is important to monitor the heart, kidneys, and brain from the time of diagnosis with Fabry disease. In both classic and non-classic Fabry disease, symptoms always worsen over time.

Although there is not currently a cure for Fabry disease, there are two Food & Drug Administration (FDA) approved medications in the United States that can help stabilize or prevent progression of the more serious health problems if started early in the disease course. Fabrazyme, or agalsidase beta, is made by a company called Genzyme Sanofi. Fabrazyme is an enzyme replacement therapy (ERT) usually given every two weeks by IV. Outside of the United States, a second ERT medication for Fabry disease made by Shire Inc. is available called Replagal (agalsidase alfa).

Recently another medication, called migalastat or Galafold made by Amicus Therapeutics was approved in the United States. GALAFOLD™ is an oral pharmacological chaperone medications indicated for the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.

In addition to ERT, there are symptom specific treatments available to help relieve some of the other health problems of Fabry disease and there are also support networks to help individuals cope with the day-to-day struggles of living with Fabry disease such as the Fabry Support and Information Group (FSIG) and the National Fabry Disease Foundation (NFDF).

There is an excellent summary about Fabry disease written for doctors at Fabry Disease- GeneReviews.

SOURCE: Emory University - Department of Human Genetics in collaboration with ThinkGenetic • https://www.thinkgenetic.com/diseases/fabry-disease/overview/557 • DATE UPDATED: 2019-01-22


Hopkin RJ, Jefferies JL, Laney DA, Lawson VH, Mauer M, Taylor MR, Wilcox WR; Fabry Pediatric Expert Panel. The management and treatment of children with Fabry disease: A United States-based perspective. Mol Genet Metab. 2016 Feb;117(2):104-13. http://www.ncbi.nlm.nih.gov/pubmed/26546059

Laney DA, Bennett RL, Clarke V, Fox A, Hopkin RJ, Johnson J, O'Rourke E, Sims K, Walter G Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2013 Oct;22(5):555-64. http://www.ncbi.nlm.nih.gov/pubmed/23860966

Laney DA, Peck DS, Atherton AM, Manwaring LP, Christensen KM, Shankar SP, Grange DK, Wilcox WR, Hopkin RJ. Fabry disease in infancy and early childhood: a systematic literature review. Genet Med. 2015 May;17(5):323-30. http://www.ncbi.nlm.nih.gov/pubmed/25232851

Fabry Disease- GeneReviews http://www.ncbi.nlm.nih.gov/books/NBK1292/

Fabry Disease- NORD http://rarediseases.org/rare-diseases/fabry-disease/

Fabry disease- A guide for the newly diagnosedhttp://genetics.emory.edu/documents/lsdc/factsheet44.pdf

Women and Fabry disease http://genetics.emory.edu/documents/lsdc/Fabry.PDF


Fabry Support and Information Group. http://www.fabry.org/

National Fabry Disease Foundation. http://www.fabrydisease.org/

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