GTR Home > Conditions/Phenotypes > Fabry's disease

Disease characteristics

Excerpted from the GeneReview: Fabry Disease
Fabry disease results from deficient activity of the enzyme α-galactosidase (α-Gal A) and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The classic form, occurring in males with less than 1% α-Gal A enzyme activity, usually has its onset in childhood or adolescence with periodic crises of severe pain in the extremities (acroparesthesias), the appearance of vascular cutaneous lesions (angiokeratomas), sweating abnormalities (anhydrosis, hypohydosis, and rarely hyperhidrosis), characteristic corneal and lenticular opacities, and proteinuria. Gradual deterioration of renal function to end-stage renal disease (ESRD) usually occurs in men in the third to fifth decade. In middle age, most males successfully treated for ESRD develop cardiac and/or cerebrovascular disease, a major cause of morbidity and mortality. Heterozygous females typically have milder symptoms at a later age of onset than males. Rarely, they may be relatively asymptomatic throughout a normal life span or may have symptoms as severe as those observed in males with the classic phenotype. In contrast, males with greater than 1% α-Gal A activity may have either (1) a cardiac variant phenotype that usually presents in the sixth to eighth decade with left ventricular hypertrophy, mitral insufficiency and/or cardiomyopathy, and proteinuria, but without ESRD; or (2) a renal variant phenotype, associated with ESRD but without the skin lesions or pain.

Associated genes

Clinical features

  • Hematuria
  • Proteinuria
  • Anemia
  • Irregular heart beat
  • Short stature
  • Hypertension
  • Hypohidrosis
  • Abnormality of the genital system
  • Respiratory insufficiency
  • Lymphedema
  • Delayed puberty
  • Left ventricular hypertrophy
  • Left ventricular septal hypertrophy
  • Coarse facial features
  • Cognitive impairment
  • Opacification of the corneal stroma
  • Seizure
  • Cataract
  • Arthralgia
  • Diarrhea
  • Malabsorption
  • Myalgia
  • Nausea
  • Anorexia
  • Reduced bone mineral density
  • Vomiting
  • Renal insufficiency
  • Abnormality of the renal tubule
  • Nephrotic syndrome
  • Nephropathy
  • Thick lower lip vermilion
  • Sensorineural hearing impairment
  • Conjunctival telangiectasia
  • Optic atrophy
  • Behavioral abnormality
  • Diabetes insipidus
  • Hyperkeratosis
  • Angiokeratoma
  • Corneal dystrophy
  • Abnormality of the hand
  • Arthritis
  • Abnormality of the mitral valve
  • Congestive heart failure
  • Hypertrophic cardiomyopathy
  • Abnormality of the aortic valve
  • Myocardial infarction
  • Coronary artery disease
  • Angina pectoris
  • Nausea and vomiting
  • Abdominal pain
  • Emphysema
  • Vertigo
  • Transient ischemic attack
  • Developmental regression
  • Fasciculations
  • Dysautonomia
  • Cerebral ischemia
  • Abnormality of the femur
  • Abnormality of lipid metabolism
  • Muscle cramps
  • Paresthesia
  • Abnormality of the endocardium
  • Abnormality of temperature regulation
  • Chronic obstructive pulmonary disease
  • Obstructive lung disease
  • Teleangiectasia of the skin
  • Glomerulopathy
  • Tenesmus
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Go to complete MedGen record for Fabry's disease

Clinical resources

Practice guidelines

  • ACMG, 2013
    ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.
  • Italian, 2010
    Nervous system and Fabry disease, from symptoms to diagnosis: damage evaluation and follow-up in adult patients, enzyme replacement, and support therapy
  • HFSA, 2010
    HFSA 2010 Comprehensive Heart Failure Practice Guideline.
  • Int'l, 2006
    Fabry disease: guidelines for the evaluation and management of multi-organ system involvement.
  • NSGC, 2002
    Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors.
  • EuroGentest, 2011
    Clinical utility gene card for: Fabry disease.

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