FAQ
WHAT IS FABRY DISEASE?
Fabry disease is an inherited lipid storage disease.
It is the result of a deficiency in the enzyme alpha-galactosidase
A found on the X chromosome (Xq22). This defect leads to the accumulation
of glycospingolipids in the plasma and lysosomes of vascular endothelial
and smooth muscle cells. This means that a fatty component of the
cell wall cannot be broken down and builds up inside the cells, especially
the cells lining the arteries and blood vessels. This accumulation
of lipid causes clogging of the blood vessels which leads to damage
to the heart (heart attack) and kidneys (kidney failure). Lipid deposits
are also found in cells of the cornea, kidney tubules, muscle fibers
of the heart, and cells of the nervous system. Lipid stores increase
with time in the blood vessels and sweat glands of the skin, and may
be the cause of the skin and perspiration problems.
Fabry disease symptoms are characterized by angiokeratomas
(telangiectatic skin lesions – reddish spots which are caused
by the dilatation of small blood vessels), hypohidrosis (diminished
perspiration), corneal and lenticular (lens) opacities, acroparesthesia
(burning, pricking or tingling in the hands or feet), and vascular
disease of the kidney, heart and/or brain.
The disease has an X-linked recessive inheritance
pattern affecting males predominately. Most female carriers are asymptomatic
(no symptoms) but some will exhibit symptoms of the disease. This
is a rare disease and the prevalence of Fabry disease in males is
1 in 40,000. A blood test should be done for both males and females
suspected of having Fabry Disease.
WHY IS THE DISEASE CALLED FABRY DISEASE?
Fabry disease is an X-linked recessive lysosomal
storage disorder characterized by a deficiency of the a-galactosidase
A enzyme. It is also known as Anderson Fabry Disease or Morbus Fabry.
Fabry disease was first described by two European
dermatologists, Johann Fabry of Dortmund, Germany and William Anderson
of London. Working independently of each other, they both reported
it in 1898. It took another 40 years before researchers connected
the symptoms to an excess of a fatty substance found in the walls
of blood vessels. The discovery of the enzyme defect causing Fabry
Disease didn’t occur until the late 1960’s.
HOW COMMON IS FABRY DISEASE?
Fabry Disease appears in two forms, Classic and
Atypical. The Classic form of the disease is estimated to affect 1
in every 40,000 males worldwide. This form may display several or
all of the symptoms described before.
At present there are no reliable figures for how
many people may have the Atypical strain. In this form there may be
no symptoms, or development of mild symptoms of cardiac disease later
in life (cardiac varient). There are no known ethnic, environmental
or economic factors involved in the occurrence of either form of Fabry
Disease.
WHY DOES FABRY DISEASE AFFECT MOSTLY MEN?
Fabry is an X-linked (or sex related) disease.
It affects men and women differently. X-linked recessive diseases,
such as Fabry, occur primarily in men. Men have one Y chromosome inherited
from their father and one X chromosome inherited from their mother.
If the X chromosome contains a gene that is defective, that man will
have inherited the disease caused by the deficiency of the gene from
his mother. A woman inherits one X chromosome from her mother and
one from her father. Even if one X chromosome is affected, she may
exhibit only very mild or no symptoms of the disease. She will, however,
be a carrier.
- • If a woman is a carrier of Fabry
Disease:
- – each son will have a 50% chance of inheriting the gene
for Fabry Disease
– each daughter will have a 50% chance of being a carrier
- • If a man has Fabry Disease:
- – each son will be unaffected, since sons do not inherit
the X chromosome from their fathers
– each daughter will be a carrier, since all daughters inherit
their father’s X chromosome
In some rare instances, there have been cases of
Fabry Disease caused by mutations of the gene from unknown causes,
unrelated to the genes of the parents.
HOW IS FABRY DISEASE DIAGNOSED?
Fabry Disease can be diagnosed by testing the activity
level of alpha-galactosidase A in the blood. Your physician can draw
the blood for the test in your home town.
If there is a family history of Fabry Disease,
testing should be done sooner rather than later in an effort to prevent
any permanent damage to the organs. Males as well as symptomatic females
should be tested.
IS THERE AN EFFECTIVE TREATMENT FOR FABRY DISEASE?
Yes, enzyme replacement therapy is available as
the first effective treatment for Fabry disease. The treatment consists
of a modified form of the alpha-galactosidase A enzyme which is given
intravenuosly, usually every two weeks. Enzyme replacement therapy
can stop progression and often improve symptoms of Fabry disease.
IS IT POSSIBLE TO DIAGNOSE FABRY DISEASE
IN UTERO?
Yes, a prenatal diagnosis for Fabry Disease can
be made if there is a family history of Fabry Disease. The level of
enzyme activity of alpha-galactosidase A is measured to determine
if a male fetus will have the affected gene. This can be determined
as early as 9 weeks into the pregnancy.
|
