Fabry Disease

Fabry disease is a rare inherited condition in which the enzyme alpha-galactosidase A is missing or weak. A fatty substance (Gb3) accumulates in cells throughout the body, particularly in the kidneys, heart, nerves and blood vessels.

The kidneys are affected early and quietly. Without treatment, men with the classic form often reach kidney failure in their 30s to 50s. Women carry the gene on one X chromosome and range from no symptoms to severe disease. Treatment works far better before scarring has set in, so early diagnosis and family screening are the priority.

Symptoms

• Burning pain in the hands and feet, often from childhood, worse with fever, heat or exercise
• Reduced sweating and heat intolerance
• Small dark red skin spots (angiokeratomas) between the navel and the thighs
• Protein in the urine and slowly declining kidney function
• Abdominal cramps and diarrhoea after meals
• A whorl pattern on the cornea seen on eye examination, which does not affect vision
• Thickened heart muscle, palpitations or breathlessness
• Stroke or mini-stroke at a young age
• Hearing loss and tinnitus

Causes and risk factors

The cause is a variant in the GLA gene on the X chromosome. A father passes it to all of his daughters and none of his sons; a mother has a 1 in 2 chance of passing it to each child. Classic variants leave almost no enzyme activity and cause childhood symptoms. Later-onset variants leave some activity and present in adult life with mainly heart or kidney involvement, sometimes discovered when unexplained CKD or a thick heart muscle is investigated.

How it is diagnosed

• Enzyme activity: Alpha-galactosidase A measured in blood or a dried blood spot. Reliable in men; often normal in affected women.
• GLA gene testing: Confirms the diagnosis, is essential in women and shows whether the variant is suitable for migalastat.
• Lyso-Gb3: A blood marker that supports the diagnosis and helps in monitoring.
• Urine albumin and eGFR: Track kidney involvement from the time of diagnosis.
• Kidney biopsy: Sometimes performed, showing characteristic layered deposits within the filter cells.
• Cardiac MRI, ECG and brain MRI: Baseline assessment of the other organs at risk.
• Family screening: Each diagnosis typically identifies several affected relatives.

Treatment options

• Enzyme replacement therapy: Agalsidase alfa or beta, or pegunigalsidase alfa, given as an intravenous infusion every 2 weeks for life.
• Migalastat: An oral chaperone capsule taken every other day, only for people with an amenable gene variant and adequate kidney function.
• ACE inhibitor or ARB: Reduces protein leak and protects the kidneys alongside specific therapy.
• Pain control: Carbamazepine, gabapentin or similar medicines for nerve pain; avoiding known triggers.
• Heart and stroke prevention: Blood pressure control, rhythm monitoring, pacemaker or defibrillator where indicated, antiplatelet therapy after stroke.
• Dialysis and kidney transplant: A transplanted kidney has normal enzyme activity and does well, but specific therapy continues to protect the other organs.

When it is urgent

Call emergency services locally for sudden weakness, facial droop or speech difficulty, chest pain, fainting or a sustained racing heartbeat. People with Fabry disease have strokes and rhythm problems at younger ages than expected, so these signs must not be dismissed.

Travelling to Türkiye for treatment

A trip can be worthwhile for diagnosis: enzyme and genetic testing, a kidney biopsy if needed, and a full organ assessment in one visit. Treatment is a different matter. Infusions every 2 weeks for life, or a very costly daily medicine funded through national programmes, must be organised in your own country. Bring family history and any earlier biopsy reports, and plan for relatives to be tested at home.

Send your reports, scans and a short history and a Clinic-Y coordinator replies within 24 hours with suitable teams and written, all-inclusive proposals side by side. Reviewing your case is free.

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