Fabry Disease Symptoms, Causes, Symptom Treatment, and Life Expectancy

  • Medical Author:
    John P. Cunha, DO, FACOEP

    John P. Cunha, DO, is a U.S. board-certified Emergency Medicine Physician. Dr. Cunha's educational background includes a BS in Biology from Rutgers, the State University of New Jersey, and a DO from the Kansas City University of Medicine and Biosciences in Kansas City, MO. He completed residency training in Emergency Medicine at Newark Beth Israel Medical Center in Newark, New Jersey.

  • Medical Editor: William C. Shiel Jr., MD, FACP, FACR
    William C. Shiel Jr., MD, FACP, FACR

    William C. Shiel Jr., MD, FACP, FACR

    Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

View the Impotence Slideshow Pictures

Fabry disease definition and facts

  • Fabry disease is a rare genetic disease with a deficiency of an enzyme called alpha-galactosidase A. The disease affects many parts of the body including the skin, eyes, gastrointestinal system, kidney, heart, brain, and nervous system.
  • Symptoms of include:
  • Fabry disease is caused by a defect on the X chromosome. X-linked genetic mutations tend to occur mostly in males, and rarely in females.
  • It's estimated that it affect1 1 in 40,000 males in the US.
  • The disease is diagnosed with a test that measures leukocyte alpha-Gal A enzyme activity.
  • Treatment for Fabry disease includes enzyme replacement therapy along with medications to treat and prevent other symptoms of the disease. Kidney transplants may be needed in severe cases when renal failure occurs.
  • The life expectancy of males with Fabry disease is about 58 years, and the life expectancy of females with the disease is just over 75 years.

What is Fabry disease?

Fabry disease is a rare genetic disease a deficiency of the enzyme alpha-galactosidase A (a-Gal A) that causes a buildup of a type of fat called globotriaosylceramide (Gb3, or GL-3) in the body. Fabry disease is classified as a type of lysosomal storage disorder. Lysosomes are isolated areas of cells that contain enzymes. In a lysosomal storage disorder these enzymes do not properly metabolize certain fatty molecules. As a result, the undigested fat molecules accumulate and impair a cell's ability to function. In Fabry disease, the alpha-galactosidase A enzymes are deficient and globotriaosylceramide accumulates, which can affect the function of the skin, eyes, gastrointestinal system, kidney, heart, brain, and nervous system.

Fabry disease is the result of a mutation of the gene responsible for making alpha-galactosidase enzyme, which is located on the X chromosome. Fabry affects mostly males though rarely females may inherit the disease.

Fabry disease is a progressive disorder and symptoms that affect the kidneys, heart, or brain most often occur when patients are age 30 to 45 years.

What causes the disease; is it genetic?

Fabry disease is a genetic disorder. A genetic disorder is caused by a mutation, or change, in a part of a person's DNA. In Fabry disease the defective gene is on the X-chromosome, which is one of two sex chromosomes. Sex chromosomes determine a person's gender at birth. Everyone inherits one sex chromosome from each parent. Mothers pass on only X chromosomes while fathers can pass on either an X or a Y chromosome. The chromosome passed on by the father then determines the sex of the offspring: females have two X chromosomes (XX), and males have one X chromosome and one Y chromosome (XY). Fabry disease affects mostly males, who receive one X chromosome with the abnormal gene. Females with Fabry disease also receive one X chromosome with the defective gene, however, since females have two X chromosomes, the normal X chromosome can offer some protection against developing the disorder.

Fabry disease is caused by a genetic mutation resulting in a deficiency of an enzyme called alpha-galactosidase A (a-Gal A). The genetic defect causes the body to not make enough of this enzyme leading to a buildup of a type of fat called globotriaosylceramide (Gb3, or GL-3) in the body cause the symptoms of Fabry disease.

How do you inherit Fabry disease?

Fabry disease is the result of what is called an X-linked inheritance, that is, the disease is caused by a defect on the X chromosome. X-linked genetic mutations tend to occur mostly in males and rarely in females.

If a mother is carrying the defective gene for Fabry disease, both male and female children have a 50% chance of inheriting it from their mother. If the father is carrying the Fabry gene, the female children will inherit the defective gene because the father passes along an X chromosome to them, but the male children, who get a Y chromosome, will not.

Females who inherit a defective X chromosome are called carriers and they may pass the genetic mutation on to their male children.

What is a Genetic Disease?

A genetic disease is caused by an abnormality in a person's genome. There are many different types of genetic inheritance including single, multifactoral, and mitochondrial. The following is a short list of genetic diseases:

  • Turner syndrome
  • Sickle cell anemia
  • Cystic fibrosis
  • Heart disease
  • High blood pressure
  • Cancer
  • Obesity

What are the signs and symptoms of Fabry disease?

Signs and symptoms include:

  • Episodes of pain and burning sensations in the hands and feet (acroparesthesias) that can be triggered by exercise, stress, fatigue, fever, or changes in weather
  • Small, dark red spots on the skin (angiokeratomas), mostly in clusters from the belly button to the knees
  • Decreased ability to sweat
  • Cloudiness of the front part of the eye
  • Problems with the gastrointestinal system
  • Ringing in the ears (tinnitus)
  • Hearing loss
  • Mitral valve prolapse
  • Abdominal discomfort
  • Frequent bowel movements after eating
  • Joint pain
  • Back pain in the kidney area

Complications of Fabry disease include kidney damage, heart disease and heart attack, and strokes.

What is the prevalence or incidence of Fabry disease?

It is estimated that Fabry disease affects 1 in 40,000 males. The prevalence of Fabry disease in females is unknown. It can affect all ethnicities, but it predominantly affects Caucasians. Late-onset forms of Fabry disease, which tend to be milder, are more common than the classic severe form diagnosed earlier in life.

What types of testing diagnoses the disease?

Fabry disease can be difficult to diagnose because it is so rare. The standard test to diagnose Fabry disease is a measurement of leukocyte alpha-Gal A enzyme activity. This test can detect the presence of the mutation for Fabry disease in males, however, it will only identify about 50% of the female carriers.

Which specialties of doctors treat Fabry disease?

Because Fabry disease can affect many different organs many specialists may be consulted:

  • Nephrologist for kidney problems
  • Cardiologist for heart problems
  • Neurologist or neurosurgeon for brain and nervous system symptoms
  • Ophthalmologist for eye problems
  • Gastroenterologist for digestive problems
  • Otolaryngologist (ear, nose, and throat specialist, or ENT) for hearing problems
  • Additionally, patients may benefit from working with physical therapists, nutritionists, and psychologists to help manage symptoms.
  • Patients may also wish to consult with genetic counselors.

What is the treatment for Fabry disease; is there a cure?

Fabry disease may be treated using enzyme replacement therapy with agalsidase-alpha (Replagal) or agalsidase beta (Fabrazyme) to help normalize kidney function, heart function, and blood supply to the brain.

Other treatments for Fabry disease are aimed at relieving individual symptoms.

What is the life expectancy for a person with Fabry disease?

The life expectancy of males with Fabry disease is about 58 years, and the life expectancy of females with Fabry disease is just over 75 years. The most common cause of death in both genders is cardiovascular disease.

Other names for Fabry disease

Fabry disease is referred to by many other names, for example:

  • Alpha-galactosidase A deficiency
  • Anderson-Fabry disease
  • Angiokeratoma corporis diffusum
  • Angiokeratoma diffuse
  • Ceramide trihexosidase deficiency
  • Fabry's disease
  • GLA deficiency
  • Hereditary dystopic lipidosis

REFERENCES:

Desnick, MD, PhD. et al. "Genetics of Fabry Disease Treatment & Management." Medscape. Updated FEb 24, 2016.
<http://emedicine.medscape.com/article/951451-treatment>

Fabry Support & Information Group (FSIG). "What is Fabry Disease."
<http://www.fabry.org/fsig.nsf/pages/fabry>

National Organization for Rare Disorders. (2015). "Fabry Disease."
<http://rarediseases.org/rare-diseases/fabry-disease/>

U.S. National Library of Medicine Genetics Home Reference. (2016, June 21). "Fabry disease." Updated Jun 28, 2016.
<https://ghr.nlm.nih.gov/condition/fabry-disease>

Waldek, S. P., et al. "Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry." Genet Med. 2009 Nov;11(11):790-6. doi: 10.1097/GIM.0b013e3181bb05bb
<http://www.ncbi.nlm.nih.gov/pubmed/19745746>

Last Editorial Review: 5/10/2017

Subscribe to MedicineNet's Men's Health Newsletter

By clicking Submit, I agree to the MedicineNet's Terms & Conditions & Privacy Policy and understand that I may opt out of MedicineNet's subscriptions at any time.

Reviewed on 5/10/2017
References
REFERENCES:

Desnick, MD, PhD. et al. "Genetics of Fabry Disease Treatment & Management." Medscape. Updated FEb 24, 2016.
<http://emedicine.medscape.com/article/951451-treatment>

Fabry Support & Information Group (FSIG). "What is Fabry Disease."
<http://www.fabry.org/fsig.nsf/pages/fabry>

National Organization for Rare Disorders. (2015). "Fabry Disease."
<http://rarediseases.org/rare-diseases/fabry-disease/>

U.S. National Library of Medicine Genetics Home Reference. (2016, June 21). "Fabry disease." Updated Jun 28, 2016.
<https://ghr.nlm.nih.gov/condition/fabry-disease>

Waldek, S. P., et al. "Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry." Genet Med. 2009 Nov;11(11):790-6. doi: 10.1097/GIM.0b013e3181bb05bb
<http://www.ncbi.nlm.nih.gov/pubmed/19745746>

Health Solutions From Our Sponsors