Fabry disease

This is part of Rare diseases.

Diagnosis: Fabry disease

Synonyms: Anderson-Fabry disease, Alpha-galactosidase A deficiency, Angiokeratoma corporis diffusum


Date of publication: 2014-10-09
Version: 2.1

ICD 10 code


The disease

Fabry disease is a lysosomal disease caused by the deficiency of an enzyme, alpha-galactosidase A. This results in certain chemical substances accumulating in cells rather than being broken down, which can result in damage to the blood vessels and certain organs. Pain is common and symptoms manifest in the skin, heart, kidneys and blood vessels of the brain. The nature and severity of the symptoms vary greatly between individuals.

Two dermatologists, Johannes Fabry in Germany and William Anderson in England, described Fabry disease independently in 1898. Other names for the disease are Anderson-Fabry disease, alpha-galactosidase A deficiency and angiokeratoma corporis diffusum.

Currently (2014), approximately seventy different lysosomal diseases have been identified. In lysosomal diseases, lysosomal function is impaired either as a result of a defect in one of the lysosome’s enzymes, or is caused by a defect in the transport proteins which carry substances into or out of lysosomes. Lysosomes are small cellular subunits present in all cells of the body except for the red blood cells, and can be described as the cell’s recycling centre. Some other examples of lysosomal diseases are: aspartylglykosaminuria, cystinosis, Danon disease, Gaucher disease, GM2 gangliosidosis, Krabbe disease, mannosidosis, metachromatic leukodystrophy, mucopolysaccharidoses I, II, III, IV, VI and VII, Pompe disease and Salla disease. Separate information on these diseases is available in the rare disease database of the Swedish National Board of Health and Welfare. Fabry disease is the second most common lysosomal disease.


The disease affects approximately two in every 100,000 people. To date, over 60 people have been diagnosed with the condition in Sweden. There are probably more people with the disease who have not been diagnosed.


The enzyme deficiency is caused by a mutation in the GLA gene. GLA controls the production of (codes for) the enzyme alpha-galactosidase A, and is located on the X chromosome (Xq22). Normally alpha-galactosidase A is present in the cell’s lysosomes, but in Fabry disease it is partially or wholly absent. The role of lysosomes is, with the help of enzymes, to take care of and break down different materials. (Enzymes are proteins which accelerate chemical reactions in the body without themselves being broken down.) In this process the constituent parts of these materials become available for re-use. Proteins, for example, are broken down into aminoacids. These newly-released “building blocks” are transported out of the lysosomes and become available to cells for the production of new substances.

In Fabry disease the important chemical substances known as glycosphingolipids (in particular globotriaosylceramide Gb3), cannot be broken down. Glycosphingolipids are particular types of fats which contain carbohydrates. They are normally found in the outer covering of the cell, the plasma membrane. As they are not broken down they are stored inside the cells. This, together with other as yet unidentified factors, leads eventually to damage to the blood vessels, kidneys, heart and peripheral nervous system. It is presumed that the pain associated with the condition is the result of the storage of globotriaosylceramide in the posterior horn of the spinal cord (where the peripheral nerves enter the spinal cord) causing injury to thin nerve fibres, which are sensitive to pain.


Fabry disease is caused by a mutated gene located on the X chromosome, which is one of the chromosomes determining sex. Men normally have one X chromosome and one Y chromosome, while women have two X chromosomes. Inherited X-linked recessive disorders usually occur only in men, being passed down via a healthy female carrier who has one normal and one mutated gene. However, in Fabry disease women can also become ill, in certain cases just as ill as males.

In girls, normally one of the two X chromosomes is inactivated in every cell. This random process of inactivation takes place at an early stage in foetal development. It means that in a female with the mutation, the healthy gene is active in approximately 50 per cent of her cells, which may be enough to prevent her from developing symptoms. Sometimes this random inactivation of one copy of the gene is associated with a larger or smaller number of mutated X chromosomes in an individual, which accounts for the great variation in symptoms among girls who have the mutation associated with Fabry disease.

Sons and daughters who have inherited the normal version of the X chromosome do not have the syndrome and do not pass on the mutation.

Figure: X-linked recessive inheritance  via a healthy female carrier

Figure: X-linked recessive inheritance via a male carrier with the disease


The disease manifests most frequently in childhood, with episodes of pain in the hands and feet, difficulties in perspiring, and changes to the skin and eyes. Symptoms arise when chemical substances which cannot be broken down are stored in different cells, above all in the blood vessels, kidney tissue, heart musculature and the cornea, as well as the nerves of the central and peripheral nervous system. The severity of the disease varies greatly between individuals, and the condition of women with the disease ranges from asymptomatic to severely ill.

Pains usually present for the first time at between seven and twelve years of age, but can also develop later in life. They are often described as an intense, burning sensation radiating out to the fingers and toes. During periods when pain is less intense there is often a slight loss of feeling and sometimes a tingling sensation. When children with the disease experience pains for the first time they may become feverish. Subsequently, the pains may increase and become more frequent, especially during periods of physical activity. Pain may be triggered by exertion or changes in temperature and humidity.

Certain people experience a continuous, moderate level of pain and experience attacks of more severe pain on particular occasions (known as Fabry crises). These episodes of severe pain can last from a few minutes to several days. They may force schoolchildren or teenagers to abstain from physical education lessons or challenging leisure pursuits, as they can trigger painful episodes. Some adults find that their condition deteriorates and that they experience more severe pain after they have drunk alcohol. Pain often diminishes over time, and in adulthood it may disappear completely.

Certain individuals with the disease sweat less than normal, while others do not sweat at all. When the weather is warm, or during periods of fever or physical exertion, this may cause problems. An impaired ability to sweat is caused by the accumulation of globotriaosylceramide in the thin nerve fibres which control the sweat glands. Other symptoms that indicate the autonomous nervous system may be affected include diarrhoea or constipation.

Small, reddish nodules (telangiectasias and angioceratomas) may appear in different places on the skin, above all in the area between the waist and the knees, and in the mouth. They often increase in number and size and with time may become disfiguring.

Glycosphingolipids may accumulate in different areas of the eye. This usually occurs in the cornea so sight is not affected. However, if this accumulation occurs in the lens capsule or in the blood vessels of the retina, in rare cases vision may be affected.

In adults, the heart, kidneys and the blood vessels of the brain are commonly affected. The lungs may also present symptoms which include obstructive lung disease, chronic bronchitis and breathlessness. There may also be problems in the gastro-intestinal tract in the form of diarrhoea, sickness, gas and pains in the side. Fingers and toes may ache and become white when cold as blood vessels contract (Raynaud’s phenomenon).

Accumulations in the kidneys lead to an impairment of kidney function. Eventually, the kidneys may cease to function, causing kidney failure. Cysts on the kidneys (renal sinus cysts and parapelvic cysts) may also develop.

The heart can be affected in a number of ways. If glycosphingolipids accumulate in coronary blood vessels, blood circulation will be impaired and may cause a heart attack. If they accumulate in the muscle cells of the heart, this organ may become enlarged and cardiac function be impaired. Sometimes these accumulations affect cardiac rhythm and the heart may beat slower or faster than normal. Heart valves, too, may be damaged in Fabry disease.

If the blood vessels of the brain are damaged by the accumulation of glycosphingolipids, this can lead to TIAs (transient ischaemic attacks) or a stroke.


Fabry disease may be suspected if a relative has the condition or if specific symptoms manifest. It often takes a very long time to be diagnosed, on average 15 years.

Fabry disease should be suspected if the individual experiences:

  • recurrent attacks of severe pain in the hands and feet
  • small red nodules (angioceratomas) on the skin
  • impaired ability to sweat
  • enlargement of the left ventricle of the heart in young adults
  • stroke of unknown origin in young adults
  • chronic kidney disease in young adults
  • multiple renal cysts
  • deposits on the cornea

In men with typical symptoms and from families where the illness is recognised, a blood test which reveals low activity of enzyme alpha-galactosidase A in white blood cells will confirm the diagnosis. DNA testing is possible, and is especially important for women whose fathers have not had Fabry disease, and for both men and women without typical symptoms or who may have below average enzyme activity.

At the time of diagnosis it is important that the family is offered genetic counselling. Carrier and prenatal diagnosis, as well as pre-implantation genetic diagnosis (PGD) in association with IVF (in vitro fertilization), are available in families where the mutation is known.


There are two specific treatments for Fabry disease involving genetically engineered alpha-galactosidase enzyme (recombinant human alpha-galactosidase alpha and beta). The enzyme is administered via a drip (an intravenous infusion) every fourteen days.

Enzyme replacement treatment can reduce disease activity levels and slow the rate of deterioration. Studies have shown that the enzyme reduces pains, and causes a marked reduction in the storage of globotriacylceramide in the skin, heart and most types of kidney cells. Enzyme replacement therapy is most effective before the kidneys have suffered much damage, with high levels of proteins being excreted in the urine. The risk of stroke does not appear to diminish, despite the enzyme reducing the accumulation of globotriacylceramide in certain places in the blood vessels. Initially, the treatment is carried out at a hospital or clinic but some people with the disease learn to carry it out themselves. It is assumed that treatment will be life-long. The most common side effect is shivering.

Pains in hands and feet often accompany attacks of fever, or occur when body temperature rises during exertion. Medication such as paracetamol or acetylsalicylic acid can be used to reduce fever and alleviate pain. Pain may also be treated with epilepsy or depression medications.

Other treatments available are:

  • laser treatment for skin problems
  • medication for cardiac insufficiency, dysrhythmia and coronaries; regular cardiac monitoring with ultrasound
  • preventive treatment for blood clots, including acetylsalicylic acid (aspirin) or other medication
  • dialysis or kidney transplantation in cases of very serious loss of kidney function.

Problems associated with Raynaud phenomenon can be alleviated by medication which widens blood vessels, or by hand cream containing one per cent nitroglycerine. People with the condition should keep their hands and feet warm in cold weather and avoid certain medications (such as betablockers) which cause the blood vessels to contract.

It is also very important to avoid smoking, as damage to the lungs in people with Fabry disease is greater than in healthy people. Smoking also exacerbates damage to the blood vessels.

High blood pressure in people with the condition, whether or not it is associated with kidney damage, is treated in the first instance by ACE inhibitors or ARB medication.

Practical advice

Cold, wet compresses, or other methods of cooling the hands, including the use of cooling ointments, can help reduce pain. Holding the hands high, sitting on them or clenching them hard are methods adopted by different individuals to reduce pain. Relaxation exercises may also help.

National and regional resources in Sweden

The Fabry Centre, Centre for Endocrinology and Metabolism (CEM), Blå Stråket 5, Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 95 56. Contact Specialist physician Dimitrios Chantzichristos, email: dimitrios.chantzichristos@vgregion.se.

Analysis of enzyme analysis

Neurochemistry Laboratory, Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 10 00. Contact Associate Professor Jan-Eric Månsson, email: jan-eric.mansson@vgregion.se.

Centre for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00. 

Resource personnel


Specialist physician Annika Reims, Centre for Inherited Metabolic Disorders, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.


Specialist physician Dimitrios Chantzichristos, Section of Endocrinology, Diabetes, and Metabolism, Sahlgrenska University Hospital/Sahlgrenska, Blå stråket 5, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 95 56, email: dimitrios.chantzichristos@vgregion.se.

Kristina Cid Käll, RN, can be contacted through the Fabry Centre (CEM), Blå stråket 5, Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 95 56.

Associate Professor Andreas Kindmark, Clinic for Metabolic Diseases, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00.

Specialist physician Mikael Oscarson, Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 70 00.

Courses, exchanges of experience, recreation

The patient association for people with Fabry disease in Sweden meets annually. See under, “Organizations for the disabled/patient associations, etc.”

Organizations for the disabled/patient associations etc.

The patient association for people with Fabry disease in Sweden is a member of Rare Diseases Sweden and collaborates with associations in other Nordic countries. Email: info@fabry.se, www.fabry.se.

Rare Diseases Sweden, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Diseases Sweden is a national association representing people with rare diseases and varying disabilities.

Courses, exchanges of experience for personnel

Courses are arranged for medical professionals. Information is available at The Fabry Centre at Sahlgrenska University Hospital in Gothenburg, Sweden. (See under “Resources.”)

Research and development

Research is ongoing at The Fabry Centre, Centre for Endocrinology and Metabolism (CEM), Sahlgrenska University Hospital/Sahlgrenska, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 95 56. In collaboration with the stroke unit at Sahlgrenska University a research project is under way to identify the occurrence of Fabry disease in people who have experienced a cryptogenic stroke. Research is in collaboration with other European countries, primarily Denmark.

Information material

Short summaries of all the database texts are available as leaflets, in Swedish only. These leaflets may be ordered or printed out. (See under “Mer hos oss” in the right hand column.)

It is possible to access further websites with information on Fabry disease through the Swedish patients’ association website www.fabry.se.

Information is available at the Centre for Rare Disorders, Oslo University Hospital HF, Rikshospitalet, NO-0424 Oslo, Norway. Tel: +47-23075340, email: sjeldnediagnoser@oslo-universitetssykehus.no, www.sjeldnediagnoser.no.


Baehner F, Kampmann C, Whybra C, Miebach E, Wiethoff CM, Beck M. Enzyme replacement therapy in heterozygous females with Fabry disease: results of a phase IIIB study. J Inherit Metab Dis 2003; 26: 617-627.

Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M et al. Agalsidase-beta therapy for advanced Fabry disease. Ann Intern Med 2007; 146: 77-86.

Desnick RJ. Enzyme replacement therapy for Fabry disease: lessons from two alpha-galactosidase A orphan products and one FDA approval. Expert Opin Biol Ther 2004; 4: 1167-1176.

El Dib RP, Nascimento P, Pastores GM. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev 2013; 28; 2.

Eng CM, Guffon N, Wilcox RW, Germain DP, Lee P, Waldek S et al. Safety and efficacy of recombinant human alpha-galaktosidase A replacement therapy in Fabry disease. N Engl J Med 2001; 345: 9-16.

Glass RB, Astrin KH, Norton KI, Parsons R, Eng CM, Banikazemi M et al. Fabry disease: renal sonographic and magnetic resonance imaging findings in affected males and carrier females with the classic and cardiac variant phenotypes. J Comput Assist Tomogr 2004; 28:158-168.

Guffon N, Fouilhoux A. Clinical benefit in Fabry patients given enzyme replacement therapy - a case series. J Inherit Metab Dis 2004; 27: 221-227.

Gupta S, Ries M, Kotsopoulos S, Schiffmann R. The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of large cohort of clinically affected heterozygous women. Medicine (Baltimore) 2005; 84: 261-268.

Hilz MJ, Brys M, Marthol H, Stemper B, Dütsch M. Enzyme replacement therapy improves function of C-, A-delta-, and A-beta-nerve fibers in Fabry neuropathy. Neurology 2004; 62: 1066-1072.

Linthorst GE, Hollak CEM, Donker-Koopman WE et al. Enzyme therapy for Fabry disease: Neutralizing antibodies toward agalsidase alpha and beta. Kidney Int 2004; 66: 1589-1595.

MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet 2001; 38: 750-760.

MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet 2001; 38: 769-775.

Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Invest 2004; 34: 236-242.

Schaefer RM, Tylki-Szymanska A, Hilz MJ. Enzyme replacement therapy for Fabry disease. A systematic review of available evidence. Drugs 2009; 69: 2179-2205.

Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T et al. Enzyme replacement therapy in Fabry disease. JAMA 2001; 285: 2743-2749.

Schiffmann R, Floeter MK, Dambrosia JM, Gupta S, Moore DF, Sharabi Y et al. Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve 2003; 28: 703-710.

Spinelli L, Pisani A, Sabbatini M, Petretta M, Andreucci MV, Pracaccini D et al. Enzyme replacement therapy with agalsidase beta improves cardiac involvment in Fabry’s disease. Clin Genet 2004; 66; 158-165.

Weidemann F, Breunig F, Beer M, Sandstede J, Turschner O, Voelker W et al. Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease. Circulation 2003; 108: 1299-1301.

Wilcox WR, Banikazemi, Guffon N, Waldek S, Lee P, Linthorst GE et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 2004; 75: 65-74.

Database references

OMIM (Online Mendelian Inheritance in Man)
Search: fabry disease

GeneReviews (University of Washington)
www.genetests.org (click on “GeneReviews”, then “Titles”)
Search: fabry disease

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the original draft is Senior Physician Jan-Ove Johansson, Sahlgrenska University Hospital, Gothenburg.

The material has been revised by Specialist Physician Dimitrios Chantzichristos, Sahlgrenska University Hospital, Gothenburg, Sweden.

The relevant organizations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2014-10-09
Version: 2.1
Publication date of the Swedish version: 2014-02-27

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se


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This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.