AssessmentsFabry disease (NORD)
Fabry disease (NORD)
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 15-year-old boy is brought to the dermatologist by his mother due to non-blanching red and purple raised spots with a rough surface on his hands, knees, chest, and genitals. The boy consistently complains of pain and burning in his hands and feet, especially in the summer. Furthermore, he has had paroxysmal episodes of severe abdominal pain beginning at age 12, the cause of which has not yet been determined. Based on the patient's history and physical presentation, which enzyme is most likely deficient in this patient?
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.