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Fabry disease – causes, symptoms, diagnosis, treatment, pathology

Fabry disease – causes, symptoms, diagnosis, treatment, pathology


Fabry disease is a rare X-linked condition
caused by mutations or pathogenic variants in the GLA gene that codes for a lysosomal
enzyme called alpha galactosidase A or alpha-gal A. The alpha-gal enzyme normally breaks down
large molecules called globotriaosylceramide or GL3 and other glycosphingolipids, so that
small parts of the big molecules can be recycled for the body to use again. Without alpha-gal,
these GL3 molecules build up inside the lysosomes, the recycling centers of the cells, causing
a variety of symptoms and health issues. Fabry disease affects males and females, and
it has two forms: classic and nonclassic/later onset. In classic Fabry disease, symptoms
start in childhood and include burning, tingling, prickling, and painful neuropathic pain in
the hands and feet, frequently triggered by exercise, fatigue, stress, or illness. There
may also be a gradual decrease of sweating in childhood until many teens and adults stop
sweating entirely. In some people living with Fabry disease, small reddish-purple rashes
called angiokeratomas appear around the lower abdomen and “bathing trunk” region of
the body. There may also be gastrointestinal symptoms like cramps, frequent bowel movements,
constipation, and diarrhea. Many patients have a whorl or verticillata in their cornea,
that can be found during a split lamp eye exam – but it doesn’t typically affect vision.
Without treatment, Fabry disease complications can include kidney disease, abnormal heart
rhythms, heart enlargement, and an increased stroke risk. Nonclassic or later-onset Fabry disease doesn’t
cause the earlier symptoms of pain and gastrointestinal issues in childhood, but some adults develop
multiple symptoms as young adults. Others may only show signs of Fabry disease in a
specific organ – like the heart or the kidneys. However, these individuals also have a higher
risk of Fabry-associated complications. Fabry disease is diagnosed differently depending
on sex. For males at risk to have Fabry disease, blood samples can be tested to see the amount
of alpha-gal A. Low alpha-gal levels prompt analysis of the GLA gene for confirmation.
In females, gene analysis should be the first test done, as many affected female have normal
levels of alpha-gal A in their blood. There are two FDA approved treatments for
Fabry disease in the United States: enzyme replacement therapy with a synthetic alpha
galactosidase A, called agalsidase beta and chaperone therapy with migalastat to help
enhance residual enzyme activity. Otherwise, treatment is aimed at Fabry associated medical
issues, like medications to help with neuropathic pain, depression, and decreasing urine protein
levels or treatments like pacemakers to help with arrhythmias, or a renal transplant for
renal failure. All right, as a quick recap – Fabry disease
is an X linked condition, caused by a change in the GLA gene, which leads to a lack of
alpha galactosidase A enzyme. Without this enzyme, large molecules like GL3 build up
and cause progressively worsening health issues. Symptoms include burning pain in the hands
and feet, angiokeratomas, and decreased sweating. Left untreated, it may cause heart and kidney
failure. Early diagnosis through genetic testing is key, and treatment can be done with synthetic
alpha galactosidase A, or chaperone therapy with migalastat.

6 thoughts on “Fabry disease – causes, symptoms, diagnosis, treatment, pathology

  1. They way you teach is not good.
    You started with the mechanism of disease then symptoms and signs. I just watched for 1 minute.
    First start with definition of the disease man.

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