Fabry disease is a rare inherited disorder (occurring in
every 1 out of 40,000 males to 1 in every 117,000 live
births) that causes widespread damage to blood
vessels due to an enzyme deficiency. An enzyme is a
type of protein that helps produce chemical reactions in
WHAT ARE THE SIGNS AN SYMPTOMS OF FABRY
There are many possible signs and symptoms of Fabry disease including fatigue, high
blood pressure, swelling (also known as edema), enlargement of the heart, pain
(generalized, in the extremities [including burning pain], or in the stomach and intestinal
area), nausea, diarrhea, lack of sweating, excess sweating (less common), foamy urine,
ringing of the ears, poor weight gain, and stroke. A stroke is a burst artery (a type of
blood vessel that carries blood away from the heart) or a blockage of an artery in the
brain. Angiokeratoms are sometimes seen, which are very small red and/or blue painless
bumps on the body. Clouding of the corneas (the clear coverings at the front of the
eyeball) can also occur.
WHAT CAUSES FABRY DISEASE?
Fabry disease is caused by a deficiency of an enzyme known as a-GAL A.
The abbreviation of a-GAL A stands for alpha galactosidase A. The
deficiency in A-GAL A is caused by a mutation (abnormality) in the
DNA (an abbreviation for deoxyribonucleic acid). DNA is a chain of
many connected genes.
Without enough of a-GALA present, it does not properly rid the body
of substance known as globotriaosylceramide. This causes this
substance to build up in the blood vessels, bodily organs, and
tissues, which impairs their normal functions. Nerve fibers can be
damaged in Fabry disease, including those that send pain impulses,
resulting in the pain that sometimes occurs in this condition.
Sometimes, the pain is causes by blood flow blockages caused by a build-up of globotriaosylceramide.
This will particularly affect small blood vessels such as those in the stomach and intestinal area. This
same build-up can affect the heart. Foamy urine in Fabry disease is caused by too much protein in the
urine. It is a sign of kidney damage, which can also occur due to excess globotriaosylceramide. The
kidneys are two organs located on each side of the spine, behind the stomach, which filter wastes from
WHY ARE MALES AFFECTEC WITH FABRY DISEASE WORSE THAN FEMALES?
The mutation in DNA that causes Fabry disease is located on the X chromosome (see below) and is
categorized as an x-linked recessive disorder. The full form of the disease (with the most severe
symptoms) only occurs in males, although females can carry the gene that causes the disease and can
experience some mild to moderate symptoms. Genes are units of material contained in a person's
chromosomes, which are structures in the cells that contain coded instructions as for how certain bodily
characteristics (such as eye color) will develop.
All of a person's genes come from his/her parents. Genes can either be dominant or recessive. A gene
that masks the effect of another gene is called a dominant gene. The gene whose expression is masked is
known as a recessive gene. In females (who have two X chromosomes), the dominant gene on one X
chromosome can mask the effect of the recessive gene on the other X chromosome. This is known as x-
inactivation and is a random process. In males, there is only one X chromosome and so if the mutation is
present on that chromosome, there is no dominant X chromosome to mask its expression, which causes
males to be more likely to experience the disorder and have worse signs and symptoms.
Each person has 23 pairs of chromosomes, meaning that there are 46 chromosomes in total. One of each
pair of chromosomes is inherited from the mother and one of each pair is inherited from the father. The
first 22 pairs of chromosomes (known as autosomes) are not involved in determining sex. The 23rd pair of
chromosomes, however, is involved in determining sex.
The 23rd pair of chromosomes consist of X and/or Y chromosomes. An X chromosome is shaped like an
X, whereas a Y chromosome is shaped like a Y. If a person has two X chromosomes, the person will
develop as a female. If a person has an X and a Y chromosome, the person will develop as a male. The X
chromosome is much larger than the Y chromosome. The X chromosome has a few thousand genes
whereas the Y chromosome has only a few genes. For this reason, most of the genes on the X
chromosome have no counterpart on the Y chromosome.
HOW IS FABRY DISEASE DIAGNOSED?
Fabry disease is often misdiagnosed (due to its rarity) but is eventually diagnosed with blood tests
measuring the a-GAL A level. This should be present in very low levels for males. However, females with
the disease can have normal levels of a-GAL A even if they have symptoms. This is because one of the
genes causing the condition may be inactivated in females. This is why the most accurate way to
diagnose the condition is to analyze the chromosomes under a microscope and study the gene that is
supposed to make the a GAL A enzyme to look for mutations. Since the kidneys can be affected in Fabry
disease, a tissue sample (biopsy) of the kidneys can be consistent with Fabry disease if too much
globotriaosylceramide is present.
HOW IS FABRY DISEASE TREATED?
There is no current cure for Fabry disease. For most people, the treatment if focused on whatever
specific signs and symptoms the patient presents with. For those who can afford it (cost = $200,000 in
U.S. dollars) there is a treatment known as enzyme replacement therapy (ERT) which attempts to infuse
the deficient enzyme into the body so it can clear the body of globotriaosylceramide (see causes section).
This treatment can slow the advancement of the disease and eliminate some signs and symptoms. There
are two types of ERTs for Fabry disease.
WHAT IS THE PROGNOSIS OF EOPLE WITH FABRY DISEASE?
Males with Fabry disease usually live for 40 to 60 years. Common causes of death in Fabry disease
include stroke, heart failure, and kidney failure.
WHAT ELSE IS FABRY DISEASE KNOWN AS?
Fabry disease is also known as Fabry's disease, Anderson-Fabry disease, angiokeratoma corporis
diffusum and alpha-galactosidase A deficiency.
WHY IS IT CALLED FABRY DISEASE?
Fabry disease was named after one of the diseaseís discovererís, Johannes Fabry, a German
dermatologist (skin doctor).