What is Fabry disease?
Fabry disease is a rare genetic disorder caused by a deficiency of the enzyme alpha-galactosidase A – also known as alpha-GAL. Alpha-GAL breaks down a fat called globotriaosylceramide (GL-3 or Gb3), which is normally produced inside healthy cells. A lack of alpha-GAL causes this substance to build up inside the cell and disturb normal cell function, causing symptoms. Fabry disease is one of a number of hereditary conditions known as lysosomal storage disorders, all of which cause problems with normal cell function.
Fabry disease is very rare, and it is roughly estimated that it affects between 1 in 17,000 and 1 in 117,000 people. Due to the way in which it is passed on through genes, men are more likely to inherit the condition than women, with roughly 1 in every 20,000 to 40,000 men thought to have the condition.
Symptoms of Fabry disease
Signs of the condition typically manifest in early childhood and develop as the person ages. The symptoms of Fabry disease are varied and some are potentially life threatening.
The following symptoms are most commonly observed in childhood and adolescence, though they may be experienced in adulthood too:
- Pain and burning sensations, particularly in the hands and feet
- Dark red spots on the skin, typically between the belly button and knees (sometimes referred to as angiokeratoma)
- Clouded vision
- Tinnitus (ringing in the ears) and general hearing problems
- Stomach, back, or kidney pain
- Gastrointestinal problems including diarrhea, vomiting, and nausea.
The following, more serious, symptoms of Fabry’s disease are more likely to appear in adulthood:
- Heart attack or heart failure
- Enlarged heart
- Kidney failure or serious renal complications
Causes of Fabry disease
Fabry disease is caused by a genetic mutation. It is an X-linked disorder, meaning that the condition only affects the X-chromosome. As females have two X-chromosomes and males just one, males stand a far higher chance of inheriting the condition from a parent, because a second X-chromosome offers some – but not total – protection against the mutation. The children of females with Fabry disease, both male and female, stand a 50 percent chance of inheriting the disorder. Female children of males with Fabry disease will always inherit the disorder, though they may not always display symptoms. Male children of males with the condition will not inherit Fabry disease.
The genetic defect leads to a lack of the enzyme alpha-galactosidase A that in turn leads to a buildup of globotriaosylceramide, a type of fat that is normally broken down as part of healthy cell function. The severity of the disorder depends on how much alpha-galactosidase the body produces. In some, this can be none at all, while in others the enzyme is present but in insufficient quantities.
Diagnosing Fabry disease
The early diagnosis of Fabry disease is important for beginning the management of the condition. This process may begin when a person displays some of the common symptoms and a doctor suspects the presence of the disorder. However, due to the rarity of Fabry disease, the initial signs of the disorder may not be recognized and the disorder left undiagnosed. If an individual or family member has observed similar symptoms in other family members and there is a suspicion of the condition, a doctor’s opinion should be sought.
Laboratory testing can confirm the presence of Fabry disease. Enzyme assay, as the method is known, measures the volume of alpha-galactosidase A in the body. For males, this involves a blood test. If the blood shows a person has low levels of the enzyme, Fabry disease can be confirmed. This test can also be carried out on females, but may not be as accurate. DNA testing is a far more accurate test for Fabry disease diagnosis in females.
Prenatal (before birth) testing for Fabry disease is also available, though this test will usually only be offered to parents with Fabry disease or those with a strong family history of the disorder.
Treatment of Fabry disease
There is no cure for Fabry disease so treatment is centered on managing the symptoms of the disorder. This can be combined with enzyme replacement therapy, which has demonstrated some success in combating the enzyme deficiency and should be started as soon as a diagnosis is made.
Enzyme replacement therapy
Enzyme replacement therapy (ERT) is aimed at reversing the abnormalities in the cells of those with Fabry disease, thereby easing the symptoms of the condition. Only in use since 2001, ERT is a relatively new treatment method for people with Fabry disease. Two medications are available for this treatment, Replagal and Fabrazyme, both of which are given through a drip into the veins. ERT has been shown to improve symptoms, as well as reducing the risk of kidney problems, stroke, and hearing loss.
Although enzyme-replacement therapy aims to treat the cause of Fabry disease, additional treatments might be needed to reduce symptoms and prevent complications.
To combat pain, doctors will generally prescribe pain relief medication such as gabapentin, carbamazepine, phenytoin and opioids. The latter are generally reserved for particularly severe pain.
The skin rash associated with Fabry disease does not generally cause discomfort but can in some cases bleed. Cosmetic treatments such as laser therapy may be used to remove or lessen the rash.
Individuals experiencing hearing loss can be fitted with a hearing aid.
Gastrointestinal symptoms such as diarrhea, vomiting and nausea are often managed with medications. Doctors may also advise people experiencing gastrointestinal problems to avoid any foods that trigger symptoms and to maintain a low-fat diet.
MedicineNet. “Fabry Disease Symptoms, Causes, Symptom Treatment, and Life Expectancy.” Accessed July 6, 2017. ↩
Medscape. “Genetics of Fabry Disease Treatment & Management.” February 24, 2016. Accessed July 7, 2017. ↩ ↩