Conditions · Metabolism (biochemistry)
Fabry disease !
In Fabry disease a lipid builds up in blood vessels, kidneys, heart and nerves: it causes hand and foot pain and, over the years, organ failure.
Updated 2026-11-01
Structures involved
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In biochemistry
- Lysosomal ganglioside breakdown: Step 4 · β-Galactosidase (galactocerebrosidase GALC or GLB1) with saposins
- Sphingolipids and sphingolipidoses
- Lysosomal storage diseases
- α-Galactosidase A
- Globotriaosylceramide (Gb3)
Why it happens
What it is
An X-linked sphingolipidosis caused by α-galactosidase A deficiency (GLA gene); globotriaosylceramide (Gb3) accumulates.
Who gets it
Estimated at 1 in 1,000 to 9,000 people; milder late-onset forms are probably more common than the classic form. It affects males and also female carriers, with variable severity.
Causes
- Variants of the GLA gene on the X chromosome
Risk factors
- Carrier mother (50% risk for each child)
- Affected father (all his daughters inherit the variant)
Pathophysiology
Without α-galactosidase A, Gb3 and lyso-Gb3 accumulate in endothelium, vascular smooth muscle, podocytes, cardiomyocytes and dorsal root ganglia. Small nerve fibre damage gives neuropathic pain and hypohidrosis; podocyte damage gives proteinuria and kidney failure; myocardial storage gives ventricular hypertrophy, fibrosis and arrhythmias; vascular damage gives early strokes. In women, random X inactivation explains the variability.
Classification
- Classic: males with little or no enzyme activity, onset in childhood
- Late-onset: residual activity, mainly cardiac or renal disease in adulthood
- Heterozygous women: from no symptoms to a classic picture
Symptoms and signs
- Burning pain in hands and feet (acroparaesthesia), sometimes in crises with fever or exercise
- Reduced sweating and heat intolerance
- Dark red papules in the swimsuit area (angiokeratomas)
- Abdominal pain and diarrhoea
- Foamy urine from proteinuria
- Palpitations and breathlessness over the years
Diagnosis
- Clinical
- Childhood acroparaesthesia, angiokeratomas and hypohidrosis; slit-lamp examination shows cornea verticillata; an X-linked family history.
- Tests
- In males, low α-galactosidase A activity in plasma, leukocytes or dried blood spots; in females, GLA gene testing; plasma lyso-Gb3; urinalysis and albumin/creatinine ratio; kidney function; ECG with short PR, hypertrophy or blocks; kidney or heart biopsy in doubtful cases.
- Imaging
- Echocardiogram with ventricular hypertrophy; cardiac MRI with low native T1 and inferolateral late enhancement; brain MRI with white matter lesions.
Treatment
- Medical
- Intravenous enzyme replacement with recombinant α-galactosidase A.
- Medical
- An oral chaperone (migalastat) for patients whose variants respond to it.
- Medical
- ACE inhibitors or angiotensin receptor blockers for proteinuria, and drugs for neuropathic pain.
- Procedure
- Dialysis or kidney transplant for kidney failure; pacemaker or implantable defibrillator for severe arrhythmias.
- Follow-up
- Regular kidney, heart and neurological follow-up, and testing of at-risk relatives.
Complications
- End-stage chronic kidney disease
- Hypertrophic cardiomyopathy, arrhythmias and heart failure
- Early stroke
- Hearing loss
Prognosis
Untreated, life expectancy in males with the classic form is shortened by kidney, heart or cerebrovascular failure. Early treatment delays organ damage.
Test yourself
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Which enzyme is missing in Fabry disease, and how is it inherited?
α-Galactosidase A (GLA gene); X-linked inheritance.
Why is enzyme measurement not enough to diagnose a woman with Fabry disease?
Random X inactivation can leave her activity normal; genetic testing is needed.
Which early triad suggests Fabry disease in a child?
Burning pain in hands and feet, reduced sweating and angiokeratomas.
Which slit-lamp finding is typical of Fabry disease?
Cornea verticillata: whorl-like opacities in the corneal epithelium.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Fabry disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); GLA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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