Fabry's disease
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Synonyms and keywords: Anderson-Fabry disease; angiokeratoma corporis diffusum universale; alpha-glucosidase A deficiency; ceramide trihexosidase deficiency; hereditary dystopic lipidosis; GLA deficiency; Sweeley-Klionsky disease
Overview
Fabry disease is an X-linked recessive inherited lysosomal storage disease, characterized by abnormal accumulation of ceramide trihexose in cardiovascular and renal systems.
Historical Perspective
It was named after Johannes Fabry.[1]
Classification
- Non-neuropathic form
- Neuropathic form
- Infantile form
- Juvenile form
Pathophysiology
- Fabry's disease follows an X-linked recessive inheritance pattern.
- A deficiency of the enzyme alpha galactosidase A causes a glycolipid known as globotriaosylceramide (also abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the blood vessels, mononuclear phagocytes, neurons, other tissues, and organs.
- This accumulation leads to an impairment of their proper function. The condition affects hemizygous males, as well as both heterozygous and homozygous females; males tend to experience the most severe clinical symptoms, while females vary from virtually no symptoms to those as serious as males.
- This variability is thought to be due to X-inactivation patterns during embryonic development of the female.
Epidemiology and Demographics
The prevalence of Fabry disease is estimated to range from 1:17,000 to 1:117,000 males in Caucasian populations.[2][3]
Diagnosis
Symptoms
- Lack of sweating (anhidrosis) or decreased sweating
- Fatigue
- Red spots on skin (angiokeratomas): tiny, painless papules that appear at any region of the body, but are predominant on the thighs, buttocks, lower abdomen, and groin.
- Burning pain of the extremities. This pain can become very intense, especially when one has a fever.
- Loss of vision or blurry vision from corneal opacities.
- Difficulty swallowing (dysphagia)
- Abdominal pain
- Greasy stools (steatorrhea)
- Chest pain and palpitations
- Delayed puberty
- Pyrexia of unknown origin
- Cyanosis of extremities on exposure to cold (Raynaud's phenomenon)
- Hearing loss
- Loss of sensations in extremities
- Telangiectasis
- Lack of coordination of muscle movement (ataxia)
Physical Examination
Appearance
- Severe growth retardation
- Extreme mental and motor retardation
Vital Signs
- Irregularly irregular pulse may be present from cardiac arrhythmias
- Blood pressure may be raised
- Pyrexia of unknown origin
Skin
Head
- Neck retraction
Eyes
- Decreased visual acuity: Loss of vision or blurring of vision
- Corneal opacities
- Fundoscopy:
- Retinal pathology may be found
Ear
- Sensorineural hearing loss may be present
Heart
- Palpation:
- Auscultation:
- S3 may be heard
- Holosystolic murmur from mitral regurgitation
Abdomen
Extremities
Neurologic
- Mental retardation
- Growth retardation
- Gradual loss of intellect
- Motor retardation
- Ataxia
- Seizures
- Spasticity
- Peripheral neuropathy
Other
- Fractures from osteoporotic bone
- Delayed puberty: lack of development of secondary sexual characteristics
- Male infertility
- Priapism
Laboratory Findings
- Blood tests
- Anemia
- Serum creatinine may be raised from chronic renal failure
- Serum urea may be elevated
- BUN may be raised
- Urinalysis:
ECG abnormalities
- AV node conduction block
- PR interval shortening
- Arrhythmias
Ultrasound
Treatment
- Until recently, treatment of Fabry's disease targeted the symptomatic effects. However, it is currently being treated at the cellular level through enzyme replacement therapy using Agalsidase alpha (Replagal) and Agalsidase beta (Fabrazyme®).
- The cost of these drugs is problematic (approximately $170,000 US a year/patient) and remains a barrier to many patients in some countries. Enzyme replacement therapy (typically infused every two weeks) may be performed in the patient's home by the patients themselves. Enzyme replacement therapy is not a cure, and must be infused recurrently for maximum benefit.
References
- ↑ Template:WhoNamedIt
- ↑ Branton MH, Schiffmann R, Sabnis SG; et al. (2002). "Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course". Medicine. 81 (2): 122–38. PMID 11889412. Unknown parameter
|month=ignored (help) - ↑ Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999). "Prevalence of lysosomal storage disorders". JAMA : the Journal of the American Medical Association. 281 (3): 249–54. PMID 9918480. Unknown parameter
|month=ignored (help)
External links
- Fabry Support & Information Group
- Template:NINDS
- Fabry's disease at NLM Genetics Home Reference
- Fabry's Disease Association