--- title: Fabry disease description: What Fabry disease is, why it thickens the heart wall and can look like hypertrophic cardiomyopathy, how it is diagnosed, why relatives should be tested and which treatment approaches clinical guidelines describe. type: disease aliases: - Anderson–Fabry disease - Anderson-Fabry disease - alpha-galactosidase A deficiency sources: - tier: guideline org: minzdrav-rf title: Болезнь Фабри year: 2026 url: https://cr.minzdrav.gov.ru/view-cr/318_3 - tier: guideline org: esc title: 2023 ESC Guidelines for the management of cardiomyopathies year: 2023 doi: 10.1093/eurheartj/ehad194 url: https://doi.org/10.1093/eurheartj/ehad194 - tier: guideline org: minzdrav-rf title: Гипертрофическая кардиомиопатия year: 2025 doi: 10.15829/1560-4071-2025-6387 url: https://cr.minzdrav.gov.ru/view-cr/283_2 - tier: reference org: msd-manuals title: Fabry Disease year: 2024 url: https://www.msdmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/fabry-disease - tier: reference org: msd-manuals title: Hypertrophic Cardiomyopathy year: 2026 url: https://www.msdmanuals.com/professional/cardiovascular-disorders/cardiomyopathies/hypertrophic-cardiomyopathy sources_checked: 2026-10-13 review: null --- Fabry disease, or Anderson–Fabry disease, is a rare inherited condition from the group of lysosomal storage diseases: the enzyme alpha-galactosidase works poorly or not at all. As a result, special fats called glycosphingolipids slowly build up in the cells of blood vessels, the nervous system, the kidneys, the heart and other organs. Heart involvement in Fabry disease is common and worsens the outlook: according to the clinical guidelines, heart disease is the leading cause of death in people with this condition. Its typical sign is a thickened wall of the left ventricle, which can make the disease look like [hypertrophic cardiomyopathy](../hypertrophic-cardiomyopathy/).

The diagram shows a small area of the left ventricular wall, close up. Heart muscle cells contain lysosomes: this is where the enzyme alpha-galactosidase works, helping to break down glycosphingolipids.

In Fabry disease, glycosphingolipids build up in the lysosomes of heart cells. The left ventricular wall thickens, either evenly, as in the diagram, or asymmetrically. The deposits themselves make up little of the heart muscle: the thickness comes mainly from enlarged muscle cells and fibrosis, a growth of connective tissue. On MRI, areas of fibrosis are most often found in the posterolateral wall of the left ventricle.

## Why it happens The disease is caused by changes (pathogenic variants) in the GLA gene, which holds the instructions for the enzyme alpha-galactosidase. This gene sits on the X chromosome, so the disease is X-linked. A man with Fabry disease passes the changed gene to all of his daughters and to none of his sons. For a woman who carries it, each son has a 50% chance of being affected, and each daughter a 50% chance of being a carrier. It is not only men who are affected. According to the clinical guidelines, 60–70% of women who carry the variant have signs of the disease, sometimes as severe as in men, although in women it is usually milder. Fabry disease is a lysosomal storage disease of the sphingolipidosis subgroup. The GLA gene maps to the long arm of the X chromosome (Xq22.1); most variants are unique to each family. Deficiency of α-galactosidase leads to accumulation of glycosphingolipids (globotriaosylceramide) in the lysosomes of vascular endothelial and smooth muscle cells, the epithelium of most organs, the nervous system and the heart. The ESC lists the absence of male-to-male transmission in the pedigree among the red flags of Anderson–Fabry disease. Clinically, there is a classic form (onset at any age, multisystem involvement) and a non-classic form (late onset, isolated involvement of the brain, heart or kidneys); the heart alone may be affected. The hypertrophy cannot be explained by deposits in myocytes and conduction tissue alone: myocyte hypertrophy and fibrosis matter more, and they are often accompanied by left ventricular diastolic dysfunction. ## Symptoms The disease shows itself in very different ways, even within one family. Heart symptoms can include chest pain like angina, although heart attacks are rare, and problems with heart rhythm and conduction, including a pulse that is too slow. The thickened wall relaxes less well, and over time [heart failure](../heart-failure/) can develop. Outside the heart, the disease causes burning pain in the hands and feet that gets worse in the heat and with exertion, small red or purple spots on the skin (angiokeratomas), reduced sweating, clouding of the cornea, protein in the urine with declining kidney function, ringing in the ears and hearing loss. People with Fabry disease have a high risk of stroke even at a young age. The first signs usually appear in the teenage years and young adulthood. The typical sign of cardiac involvement is left ventricular hypertrophy; atrial and ventricular arrhythmias and conduction disturbances are common. Angina is more common with left ventricular hypertrophy, although myocardial infarction is rarely diagnosed; the heart is affected as in small-vessel coronary disease. Valve changes are common but usually of no clinical significance; the ESC describes mitral and aortic valve thickening with mild-to-moderate regurgitation. The hypertrophy may be concentric or asymmetric; four morphological phenotypes are described: no wall thickening, concentric, asymmetric (with septal hypertrophy) and predominantly apical hypertrophy; increased right ventricular free wall thickness also occurs. Among the cardiac red flags the ESC lists a short PQ interval in young patients, atrioventricular blocks in adult patients, bradycardia, chronotropic incompetence, hypertrophy of the papillary muscles and left ventricular hypertrophy with normal systolic function. Outside the heart: neuropathic pain (small fibre polyneuropathy), transient ischaemic attacks and strokes at a young age, proteinuria as the first sign of nephropathy followed by declining kidney function up to end-stage disease, and whorl-like corneal opacity (cornea verticillata). Without treatment, death usually occurs in the fourth or fifth decade of life from cardiovascular or cerebrovascular complications or kidney failure. ## How it is diagnosed Fabry disease should be considered in anyone whose left ventricular wall is thickened for no clear reason and in anyone who has had a stroke at a young age. The heart is checked with an [ECG](../../diagnostic/ecg/), a [heart ultrasound (echocardiography)](../../diagnostic/echocardiography/), [Holter monitoring](../../diagnostic/holter-monitoring/) and 24-hour blood pressure monitoring; cardiac MRI is done when needed. The diagnosis is confirmed by blood tests: enzyme activity, the level of a substance called lyso-Gb3, and a genetic test for changes in the GLA gene. In women, enzyme activity often stays normal, so the genetic test is especially important for them. Once the disease is found in one person, testing relatives is recommended so that the disease can be detected at an early stage. Brothers and sisters and all relatives on the mother's side should be told they need testing; for a man with the disease, his mother and daughters are tested too. Diagnostic criteria in males are reduced α-galactosidase activity in blood, raised lyso-Gb3 and a pathogenic GLA variant in the hemizygous state; in females enzyme activity is often normal, and lyso-Gb3 rises much less. The ESC suggests screening males with lyso-Gb3 and, in females and for diagnostic confirmation, genetic testing for GLA variants. Hypertrophic cardiomyopathy is diagnosed when left ventricular hypertrophy cannot be attributed to infiltrative disorders or abnormal loading conditions; Fabry disease is one of the HCM phenocopies, and genetic testing helps to exclude it. On cardiac MRI, Anderson–Fabry disease is characterised by low native T1 and late gadolinium enhancement in the basal and mid segments of the posterolateral (inferolateral) wall; in areas of fibrosis T1 may "pseudonormalise". Among laboratory red flags the ESC lists elevated high-sensitivity troponin and NT-proBNP; the Russian Ministry of Health guideline recommends measuring troponin to detect cardiac involvement. Family screening with genetic testing is recommended, as is screening of high-risk groups: people with early stroke, kidney failure and hypertrophic cardiomyopathy. If a pathogenic variant has been found in the family, the ESC recommends offering cascade genetic testing, with pre- and post-test counselling, to adult relatives. ## How it is treated The treatment aimed at the cause of the disease is enzyme replacement therapy: the missing enzyme, made in a laboratory, is given regularly into a vein. In Russia, the decision on this therapy is made by a federal medical centre experienced in caring for people with Fabry disease. In studies it reduced pain, reduced left ventricular wall thickening and stabilised kidney function. The earlier the diagnosis, before irreversible organ damage, the more effective the treatment, but starting it at any stage helps: it slows the disease and eases symptoms. For some people with particular gene variants there is another approach: a medicine taken as tablets that stabilises the body's own enzyme. Complications of the disease are treated at the same time. Adults with conduction problems, a pulse that is too slow or [ventricular tachycardia](../ventricular-tachycardia/) may need a pacemaker or an implantable cardioverter-defibrillator. A person with Fabry disease is followed up regularly by a cardiologist. The doctor decides together with the patient which treatment is needed. Enzyme replacement therapy with recombinant α-galactosidase A has been developed as disease-specific treatment; all patients also receive symptomatic treatment of the main complications. Under the Russian Ministry of Health guideline, the decision to start enzyme therapy is made by a federal medical centre; drugs and eligibility criteria are not given here. An alternative in some patients is an oral pharmacological chaperone that binds to and stabilises specific mutant forms of α-galactosidase. A pacemaker or cardioverter-defibrillator for conduction disturbances, bradyarrhythmia and ventricular tachycardia is implanted in line with the clinical guidelines for those disorders. The ESC states that contrast-enhanced cardiac MRI should be considered for serial follow-up and assessment of therapeutic response. Care is multidisciplinary: cardiologist, nephrologist, neurologist, ophthalmologist, audiologist, gastroenterologist and dermatologist. ## When to call an ambulance Fabry disease develops slowly, but people with it have a high risk of stroke even at a young age, and rhythm and conduction problems of the heart are common. The Russian Ministry of Health guideline names acute and life-threatening conditions as a reason for emergency hospital admission. If there are signs of a stroke (sudden weakness or numbness on one side of the body, difficulty speaking, a drooping face), call your local emergency number (112 in the EU, 911 in the US and Canada, 999 in the UK) straight away. A slow pulse, dangerous rhythm problems and worsening breathlessness are covered in the articles on [atrioventricular block](../av-block/), [ventricular tachycardia](../ventricular-tachycardia/) and [heart failure](../heart-failure/). As with any heart condition, call an ambulance for fainting, chest pain or severe breathlessness: this is the site's general safety rule, repeated at the bottom of every page.