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 (hypohidrosis), whorls in the cornea of the eyes (cornea verticillata), reddish-purplish skin rashes (angiokeratomas), burning pain in the hands and feet (neuropathic pain), problems in the heat and cold, frequent diarrhea and constipation, protein in the urine, and slow heartbeat (bradycardia). Without treatment, Fabry-related health problems will worsen leading to heart disease, kidney disease, and increased risk for strokes. Fabry disease occurs when a person's body does not make enough of an enzyme called alpha-galactosidase A (alpha-Gal) due to changes or mutations in the GLA gene. When alpha-gal is not working, substances called glycolipids [globotriaosylceramide (GL-3 or GB3) and lyso-globotriaosylceramide (Lyso-GL3 or LysoGB3)] build up in the body's lysosomes (the "recycling centers" of the cell). This storage leads to narrowed blood vessels, inflammation, and 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 symptoms but is commonly divided into two types, "classic" and "non-classic" or "later 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 2-10 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 disease, heart disease, and increased stroke risk 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. 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.

Currently there is no cure for Fabry disease, however, 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's course. Fabrazyme®, or agalsidase beta, is an enzyme replacement therapy (ERT) usually given every two weeks by IV to breakdown the stored glycolipids in the body. Fabrazyme® is a treatment that can be given to individuals with any mutation or change in the GLA gene. Migalastat or Galafold® is pill taken every other day that is designed to help an individual with Fabry disease's own enzyme work more effectively (chaperone therapy). Galafold® only works for specific mutations in the GLA gene that are considered "amenable". Individuals with Fabry disease can talk to their doctors to learn if they may be able to take Galafold and check to see if their GLA change is considered amenable at the GLA mutation search website.

Outside of the United States, a second ERT medication for Fabry disease is available called Replagal® (agalsidase alfa). Replagal® is a treatment that can be given to individuals with any mutation or change in the GLA gene.

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.

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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

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National Fabry Disease Foundation. (n.d.). Retrieved November 22, 2019, from http://www.fabrydisease.org.

Fabry Support & Information Group. (n.d.). Retrieved November 22, 2019, from http://www.fabry.org.

Fabry disease revisited: Management and treatment recommendations for adult patients. Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, Eng C, Hopkin RJ, Laney D, Linhart A, Waldek S, Wallace E, Weidemann F, Wilcox WR. Mol Genet Metab. 2018 Apr;123(4):416-427. doi: 10.1016/j.ymgme.2018.02.014. Epub 2018 Feb 28. Review. https://www.sciencedirect.com/science/article/pii/S1096719217307680?via%3Dihub Retrieved 12DEC19.

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