Fabry at a glance
- Affects about 1 in 40,000 to 60,000 males1
- Fabry also affects females, although the prevalence is unknown1
- Caused by a mutation in the GLA gene
- Characterized by a toxic buildup of globotriaosylceramide, or Gb3
- Pain and pain crises (recurrent, abrupt episodes of pain that can be mild to severe)
- Impaired sweating
- Exercise intolerance
- Gastrointestinal symptoms such as nausea, vomiting and diarrhea
- Ankiokeratomas (small, dark spots on the skin, caused by dilation of capillaries near the surface of the skin)
- Hearing loss
- Abnormal appearance of the cornea
- Progressive kidney disease
- Increased risk of stroke
- Heart disease
- Cognitive decline
Generally, Fabry disease consists of two forms, classic and late-onset, also referred to as severe form and mild form, respectively. The mild, late-onset form is suggested to be more common.2
Left untreated, Fabry disease substantially shortens life expectancy.
The standard of care for treating Fabry disease is enzyme replacement therapy, or ERT.
ERT slows but does not halt the overall progression of disease. The body starts to break the enzyme down immediately after treatment so people on ERT typically receive lifelong biweekly infusions.
Even on the standard of care, people with Fabry disease have a significantly shortened life expectancy and may experience debilitating symptoms that reduce their quality of life.
At AVROBIO, we are developing a new approach that could halt or reverse Fabry disease with a single dose.
Fabry disease is caused by a mutation in a single gene known as GLA.
This mutation affects the normal production of an enzyme called alpha-galactosidase A (α-Gal A), which is needed to break down a complex cell lipid called globotriaosylceramide (Gb3 or GL3).
Since lysosomes can’t adequately break down Gb3 without the α-Gal A enzyme, it accumulates in cells throughout the body. This can damage tissues and cause the progressive signs and symptoms of Fabry disease.1 People with Fabry disease may also have elevated levels of globotriaosylsphingosine (lyso-Gb3) in their plasma.
As the disease progresses, irreversible organ damage can result in potentially life-threatening kidney failure, cardiac disease, and stroke.2
Fabry is a genetic disease passed down through an X-linked inheritance pattern. This means that the defective GLA gene is on the X chromosome. Mothers with a single copy of the GLA gene have a 50/50 chance of passing on the faulty gene to each of their children. Fathers affected with Fabry will pass the faulty gene to their daughters, but not their sons.
*These links are provided for informational purposes only. AVROBIO is not affiliated with any of these institutions and is not responsible for any of the content on their websites.
Learn about our Fabry clinical trials
AVROBIO is conducting a Phase 2 study of our investigational gene therapy for Fabry disease (AVRO-RD-01). To enroll in this study, individuals must be between 16 and 50 years old (in Australia and Canada) or between 18 and 50 years old (in the United States) at the time of screening with a confirmed diagnosis of classic Fabry disease (defined as <1% of normal AGA enzyme in leukocytes). Eligibility is restricted to those who have never received chaperone therapy and have not received enzyme replacement therapy in the last 10 years. There are additional eligibility requirements as well.
- Fabry disease. NIH. https://ghr.nlm.nih.gov/condition/fabry-disease#sourcesforpage. Accessed June 16, 2020.
- Spada, Marco et al. High incidence of later-onset fabry disease revealed by newborn screening. American journal of human genetics vol. 79,1 (2006): 31-40. doi:10.1086/504601.
- Garman SC, et al. The molecular defect leading to Fabry disease: Structure of Human α-Galactosidase. J Molec Biol. 2004;337(2): 319-335.
- Germain DP. Fabry disease. Orphanet (2012). https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=324&lng=EN.