HistoryThis section has been translated automatically.
DefinitionThis section has been translated automatically.
X-linked, rare lysosomal storage disease (see lysosome below) with deficiency of lysosomally localized alpha-galactosidase A, with neurological, nephrological cardiac and dermatological (small papular angiomas in about 70% of patients) symptoms.
You might also be interested in
Occurrence/EpidemiologyThis section has been translated automatically.
Incidence: 1/3.100 live births
EtiopathogenesisThis section has been translated automatically.
X-linked recessive mutation of the alpha-galactosidase A gene (alpha GAL), which is mapped on gene locus Xq22 The consequence is a deficiency of alpha-galactosidase A and leads to an accumulation of glycosphingolipids, preferably globotriaosylceramides and galabiosylceramides, in the vascular endothelia, but also in other cells.
ManifestationThis section has been translated automatically.
LocalizationThis section has been translated automatically.
Umbilical region (leading symptom), gluten, scrotum, trunk, rarely extremities. Rare is an involvement of the oral mucosa and the conjunctiva.
Clinical featuresThis section has been translated automatically.
- In the first years of life (usually beginning in schoolchildren), diffuse pain symptoms and paresthesias of the extremities, angiokeratomas and hypohidrosis are the main clinical manifestations.
- Integument (70% of patients): Multiple, symmetrically distributed, 1-3 mm large, purple-red to black-blue, only partially hyperkeratotic papules. The manifestation may be very discreet or absent. Clusters of capillaries of the nail fold as a possible precursor of an angiokeratoma. Hypo- or anhidrosis, therefore temperature increase during physical exertion; increased sensitivity to sudden temperature changes.
- In the further course, superficial symptoms of vascular involvement, e.g. heart failure due to cardiovascular changes(hypertrophic cardiomyopathy), progressive renal failure, nephrogenic hypertension and cerebral insults.
- Eye involvement: vertebral, subepithelial, yellow-brown corneal clouding lines (Cornea verticillata in 80% of cases), retinal vessel aneurysms, ampullae of the conjunctival veins.
- Neurological symptoms: paresthesias, temperature-dependent pain crises of the extremities (acroparesthesias) which decrease from the 30th LJ, headaches, pareses, cerebral hemorrhages.
LaboratoryThis section has been translated automatically.
Determination of globotriaosylceramide (Gb3) in blood (norm: < 2.3ug/l) and urine.
Complementary: Determination of the α-galactosidase A activity in leukocytes, serum, tear fluid.
In hemicygotes no or significantly reduced enzyme activity; in heterozygous women possibly no or slight reduction of enzyme activity - nevertheless, clinical symptoms cannot be excluded!
Note: Women represent a genetic mosaic: in one part of the body cells the functional X chromosome is switched on, in another part it is switched off. Women also fall ill, but later with much less severe symptoms.
Note: There are also polymorphisms without disease value.
HistologyThis section has been translated automatically.
Differential diagnosisThis section has been translated automatically.
TherapyThis section has been translated automatically.
Enzyme replacement therapy: Agalsidase alpha (Replagal) 0.1 mg/kg bw over 40 minutes or Agalsidase beta (Fabrazyme) 1 mg/kg bw over 2-4 hours at regular (usually 14-day) intervals. Both preparations often cause at least a stagnation of the course of the disease, decrease of acroparaesthesia and improvement of the quality of life. Indications of improvement of heart and kidney insufficiency. Furthermore, symptomatic treatment of cardiovascular, pulmonary and muscular disorders.
Progression/forecastThis section has been translated automatically.
Untreated infaust. Lethal outcome between 30 and 50 years of age due to cardio- and renovascular complications (uremia or vascular insults). Under therapy probably significant improvement of the prognosis. With late-onset variants normal life expectancy.
Note(s)This section has been translated automatically.
Diagnosis often only in adulthood with progression of the clinical symptoms. In case of suspected disease interdisciplinary approach with molecular genetic analysis, histology, bone marrow biopsy, urine sediment (Maltese crosses: polarization microscopic birefringent ceramide crystals). Eye examination with slit lamp: subepithelial deposited glycosphingolipids.
Capillary microscopy: tufts of some capillaries in 2 to 5 loops and their elongation. Medium plexus visibility (plexus score 2 according to Maricq). Pathological capillaroscopy may be an indication of a systemic vascular change which may occur without lipid deposition in the endothelial cells. The changes are similar to those in systemic collagenosis.
Prenatal diagnosis: chorionic villus sampling in 10th-12th weeks or amnioscentesis in 15th-18th weeks.
LiteratureThis section has been translated automatically.
- Anderson W (1898) A case of angio-keratoma. Brit J Derm 10: 113-117
- Bengtsson BA et al (2003) Enzyme replacement in Anderson-Fabry disease. Lancet 361: 352
- Desnick RJ et al (2003) Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138: 338-346
- Fabry J (1898) A contribution to the knowledge of Purpura haemorrhagica nodularis (Purpura papulosa haemorrhagica Hebrae). Arch Derm Syphil (Berlin) 43: 187-200
- Frank J et al (1996) Angiokeratoma corporis diffusum universale (Fabry's disease). Dermatologist 47: 776-779
- Frustaci A et al (2001) Improvement in cardiac function in the cardiac variant of Fabry's disease with galactose-infusion therapy. N Engl J Med 345: 25-32
- Gahl WA (2001) New therapies for Fabry's disease. N Engl J Med 345: 55-57
- Gerbig A et al (1997) Capillary microscopy in angiokeratoma corporis diffusum. Dermatologist 48: 505.
- Laxmisha C et al (2003) Cutaneous variant of angiokeratoma corporis diffusum. Dermatol Online J 9:13
- Koch N et al (2015) Erythematous papules in a 26-year-old patient. Dermatologist 66: 868-880
- Mehta A (2009) Enzyme replacement therapy with agalsidase alfa in patients with Fabry`s disease. Lancet 374: 1986-1996
- Mohrenschlager M et al (2001) Skin manifestations of Fabry disease. JAMA 286: 1315
- Pastores GM, Thadhani R (2001) Enzyme-replacement therapy for Anderson-Fabry disease. Lancet 358: 601-603
- Peters FP et al (2001) Anderson-Fabry's disease: alpha-galactosidase deficiency. Lancet 357: 138-140
- Pieroni M et al (2003) Early detection of Fabry cardiomyopathy by tissue Doppler imaging. Circulation 107: 1978-1984
- Waldek S et al (2003) PR interval and the response to enzyme-replacement therapy for Fabry's disease. N Engl J Med 348: 1186-1187
Incoming links (37)Anderson-fabry disease; Anderson, william; Angiokeratoma corporis diffusum, idiopathic; Angiokeratoma universale; Angioma seniles; Angioma seniles; Angioma serpiginosum; Angioma serpiginosum; Aspartyl glucosaminuria; Beta-mannosidosis; ... Show all
Outgoing links (14)Acanthosis; Angiokeratomas (overview); Angioma; Cardiomyopathy hypertrophic; Collagenoses; Heart failure; Hereditary haemorrhagic telangiectasia; Hypohidrosis; Lysosome; Mibelli's angiokeratoma; ... Show all
Please ask your physician for a reliable diagnosis. This website is only meant as a reference.