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Overview
Alpha-galactosidase A (a-Gal A) deficiency is a rare genetic disorder known as Fabry disease that results in an accumulation of globotriaosylceramide (Gb3, or GL-3) in the body. Lysosomal storage disorders, such as Fabry disease, fall under this category.
Enzymes are found in isolated regions of cells called lysosomes. These enzymes do not properly metabolize specific fatty compounds in lysosomal storage disorders. Because of the accumulation of undigested fat molecules, a cell's capacity to operate is hampered. Globotriaosylceramide builds up due to the alpha-galactosidase A enzymes being lacking in Fabry disease, which can impair the function of the skin, eyes, gastrointestinal tract, kidneys, heart, brain, and neurological system.
The gene that produces the alpha-galactosidase enzyme, which is found on the X chromosome, is mutated in Fabry disease. Although infrequently, Fabry can be inherited by females, it primarily affects males.
Between 30 and 45 years old is the most typical age range for the onset of the kidney, heart, and brain symptoms of Fabry disease.
Patients with Fabry disease lack the enzymes necessary to metabolize lipids or fats.
The risk of heart attack, stroke, and renal failure is increased when these fats accumulate in blood arteries and tissue. Parents pass on this hereditary issue to their offspring. Serious problems can be avoided with oral chaperone therapy and enzyme replacement.
One in 40,000 males are thought to be affected with Fabry disease. It is unknown how often Fabry disease is in females. All races can be affected, but Caucasians are disproportionately affected. Compared to the classic severe form of Fabry disease that is discovered early in life, late-onset variations, which tend to be milder, are more prevalent.
Consulting Doctor
You or your child will visit a geneticist (a specialist in genetics), a cardiologist (a specialist in the heart), a nephrologist (a specialist in kidneys), a neurologist (a specialist in the brain and nerve system), and a gastroenterologist (a specialist in the digestive tract, stomach, and intestine).
Numerous specialists may be visited due to the fact that Fabry disease can affect a wide range of organs:
specialist in renal disease
cardiac surgeon for heart issues
Neurosurgeon or a neurologist for symptoms of the neurological system and brain
Ophthalmologists treat eye conditions
For stomach issues, see a gastroenterologist
For hearing issues, consult an otolaryngologist (ENT specialist).
In order to control their symptoms, people may also find it helpful to engage with psychologists, dietitians, and physical therapists.
Symptoms
Some warning signs and symptoms are:
Acroparesthesias are episodes of pain and burning in the hands and feet that can be brought on by physical activity, stress, exhaustion, fever, or climatic changes.
Angiokeratomas are tiny, dark-red skin lesions that typically appear in groups from the belly button to the knees.
reduced sweating ability cloudiness in the front of the eye
stomach and digestive system issues
Tinnitus, a ringing in the ears
loss of hearing
Mitral valve stenosis
Uncomfortable stomach
frequent bowel motions following a meal
aching joints
back discomfort near the kidneys
Causes
A genetic disorder is fabry disease. A mutation, or change, in a person's DNA results in a genetic condition.
One of the two sex chromosomes, the X-chromosome, has the faulty gene that causes Fabry disease.
A person's gender at birth is determined by their sex chromosomes. Fathers can transmit either an X or a Y chromosome, whereas mothers can only transmit X chromosomes.
Males have one X chromosome and one Y chromosome (XY), whereas females have two X chromosomes (XX). The chromosome that the father passes on then determines the sex of the kid.
Most people with Fabry disease are males, who have one X chromosome carrying the defective gene.
Since females have two X chromosomes, the normal X chromosome can provide some protection against acquiring the condition. Females with Fabry disease also have one X chromosome with the faulty gene.
An enzyme termed alpha-galactosidase A (a-Gal A) is deficient in Fabry disease due to a genetic mutation. The body does not produce enough of this enzyme due to the genetic abnormality, which causes the body to accumulate globotriaosylceramide (Gb3, or GL-3) in the body, which produces the symptoms of Fabry disease.
The term "X-linked inheritance" refers to the fact that Fabry disease is brought on by a flaw in the X chromosome. Rarely do X-linked genetic mutations affect females, which makes them more common in males.
Both male and female children have a 50% risk of inheriting Fabry disease from their mothers if the mother carries the faulty gene for the condition. The male children, who receive a Y chromosome, do not acquire the Fabry gene if the father carries it. However, the female children, who receive an X chromosome from the father, do.
Women who inherit a damaged X chromosome are known as carriers, and they run the risk of passing the genetic mutation to their male offspring.
Treatment
Enzyme replacement therapy with agalsidase-alpha or -beta may be used to treat Fabry disease in an effort to restore kidney, heart, and blood flow to the brain to normal levels.
Other Fabry disease therapies focus on treating specific symptoms.
It may be possible to avoid episodes of pain and burning feelings (acroparesthesias) by using phenytoin, carbamazepine, or gabapentin. For very bad pain, opioids may be administered.
To prevent recurrent ischemic strokes, antiplatelet medications such aspirin, ticlopidine, clopidogrel, and aspirin-dipyridamole are recommended.
Cardioembolic strokes can be prevented by taking warfarin.
Hemodialysis and kidney transplantation may be required in cases of severe Fabry disease that has advanced to renal failure.
Among the medications that can ease and treat gastrointestinal problems include pancrelipase, metoclopramide, loperamide, and H2 blockers like cimetidine, famotidine, and others.
When kidney disease causes high levels of protein in the urine (proteinuria), ACE inhibitors and/or blockers are administered.
Antihypertensive drugs may be provided to patients with high blood pressure (hypertension), and they should maintain blood pressure under control.
Treatment for high cholesterol is also necessary.
Patients should also have a healthy lifestyle that includes a balanced diet, exercise, and no smoking. The major cause of death in both sexes is heart disease.
Prognosis
Males with Fabry disease have a life expectancy of about 58 years, and females with Fabry disease have a life expectancy of slightly over 75 years.
Tests Required for Diagnosis
Due to its rarity, Fabry disease can be difficult to diagnose. Measuring the activity of the leukocyte alpha-Gal A enzyme is the standard procedure for Fabry disease diagnosis. This test can identify male carriers of the Fabry disease mutation, however it only detects roughly 50% of female carriers.
