Difference between revisions of "Fabry Disease 2012"
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=== Atypical variants === |
=== Atypical variants === |
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| − | It is believed that late onset variants mostly with specific mutations are underdiagnosed, because of the missing typical early onset symptoms like acroparesthesia and cornea opacity. |
+ | It is believed that late onset variants mostly with specific mutations are underdiagnosed, because of the missing typical early onset symptoms like acroparesthesia and cornea opacity. According to [ Rolfs et el.] |
| − | + | '''Cardiac variant''' |
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This variant does not affect patients until their sixth to eighth decade. Usually a hypertrophic cardiomyopathy is diagnosed. Besides from a mild to moderate proteinuria, due to accumulated Gb-3 in the podocytes, no involvement of the kidney is observed. |
This variant does not affect patients until their sixth to eighth decade. Usually a hypertrophic cardiomyopathy is diagnosed. Besides from a mild to moderate proteinuria, due to accumulated Gb-3 in the podocytes, no involvement of the kidney is observed. |
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| − | + | '''Renal variant''' |
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Many patients with this variant are misdiagnosed, because about 80% of them do not show any signs of angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities. However they had moderate to severe left ventricular hypertrophy. |
Many patients with this variant are misdiagnosed, because about 80% of them do not show any signs of angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities. However they had moderate to severe left ventricular hypertrophy. |
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Revision as of 17:18, 20 April 2012
Contents
Summary
Intelligenter Inhalt hier
Phenotype
As almost each family has its own private mutation, phenotypes of affected persons can be very variable. In general, with increasing age symptoms become more severe. This effect is due to more and more accumulated glycosphingolipids that cannot be converted by the dysfunctional enzyme. The built up globotriaoslyceramide (Gb3) and related glycosphingolipids in the lysosomes, tissues, blood vessels and organs lead to a malfunction of major organs in the body starting at an age of 30 - 35 (see picture on the right). Thus untreated patients die approximately 10 - 20 years early (females and males, respectively).
Symptoms (onset)
Childhood
- Acroparesthesia (Numbness in extremities)
- Hypohidrosis (decreased sweating)
- Cornea opacity
Acroparesthesia is signaling the clinical onset of Fabry Disease. It is caused by deposited glycosphingolipids in the small blood supplying vessels of the peripheral nerves. Another very typical symptom for Fabry Disease is the whorled streaks and cloudiness of the eye (cornea opacity) resulting from deposits of granular material on the posterior lens capsule.
Adolesence
- Gastro Intestinal Manifestation - GIM (nausea, vomitting)
- Angiokeratoma
- Depression
- Heat/cold intolerance
- Fatigue
The GIM results from accumulated Gb-3 in small intestinal vessels and autonomic ganglia of the intestinal. Eventually this often leads to a weight loss of the patient. From early stages on psychosocial manifestations like depression and fatigue lead to a degression of life quality.
Adulthood
- Renal Disease
- Proteinuria (excess of serum proteins in the urine)
- Progressive renal insufficiency
- End-stage renal disease
- Cardiac Disease
- Hypertension (high blood pressure)
- Cardiomyopathy
- Central Nervous System Disease
- Headache
- Stroke
- Ischaemic cerebrovascular events
- Binswanger’s Disease (Vascular dementia)
According to FOS, the most common cause of death were renal failure (males) and cerebrovascular disease (females), whereas Waldek et al claim that the principal cause of death is cardiovascular disease. Most of these diseased patients had received a kidney transplant. Again, all these symptoms are in consequence of progressive glycosphingolipid deposition mostly in vessels and in the lysosomes.
Atypical variants
It is believed that late onset variants mostly with specific mutations are underdiagnosed, because of the missing typical early onset symptoms like acroparesthesia and cornea opacity. According to [ Rolfs et el.]
Cardiac variant This variant does not affect patients until their sixth to eighth decade. Usually a hypertrophic cardiomyopathy is diagnosed. Besides from a mild to moderate proteinuria, due to accumulated Gb-3 in the podocytes, no involvement of the kidney is observed.
Renal variant Many patients with this variant are misdiagnosed, because about 80% of them do not show any signs of angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities. However they had moderate to severe left ventricular hypertrophy.
Cross-references
- HGMD
- KEGG Disease
- OMIM
- Wikipedia
- Fabry Registry
- NCBI Bookshelf, Fabry Disease, A. Mehta and D. Hughes
- Fabry Outcome Survey FOS
- Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet Med. 2009;11:790–6.
Biochemical disease mechanism
Cross-references
Mutations
Reference sequence
Reference Sequence of α-galactosidase A from Uniprot entry P06280
>gi|4504009|ref|NP_000160.1| alpha-galactosidase A precursor [Homo sapiens] MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFM EMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNK TCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWP FQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQ VTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWA VAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT MQMSLKDLL
