関: hyperoxaluria

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/11/16 21:15:26」(JST)

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Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition.

Causes

Type I (PH1) is associated with AGXT protein, a key enzyme involved in breakdown of oxalate. PH1 is also an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect: instead of being trafficked to peroxisomes, it is targeted to mitochondria, where it is metabolically deficient despite being catalytically active. Type II is associated with GRHPR.^[1] It is also a complication of jejunoileal bypass, or in any patient who has lost much of the ileum with an intact colon. This is due to excessive absorption of oxalate from the colon.^[2]

Treatment

The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation. A child with primary hyperoxaluria was treated with a liver and kidney transplant.^[3] A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver.

Controversy

Perhaps the key difficulty in understanding pathogenesis of primary hyperoxaluria, or more specifically, why AGXT ends up in mitochondria instead of peroxisomes, stems from AGXT's somewhat peculiar evolution. Namely, prior to its current peroxysomal 'destiny', AGXT indeed used to be bound to mitochondria. AGXT's peroxisomal targeting sequence is uniquely specific for mammalian species, suggesting the presence of additional peroxisomal targeting information elsewhere in the AGT molecule. As AGXT was redirected to peroxisomes over the course of evolution, it is plausible that its current aberrant localization to mitochondria owes to some hidden molecular signature in AGXT's spatial configuration unmasked by PH1 mutations affecting the AGXT gene.

Types

Primary hyperoxaluria
Enteric hyperoxaluria
Idiopathic hyperoxaluria
Oxalate poisoning

References

^ "Primary hyperoxaluria - Genetics Home Reference".
^ Surgery PreTest Self-Assessment and Review, Twelfth Edition
^ India News & Business - MSN India: News, Business, Finance, Sports, Politics & more. - News

External links

GeneReviews/NIH/NCBI/UW entry on Primary Hyperoxaluria Type 1

UpToDate Contents

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1. 原発性高シュウ酸尿症 primary hyperoxaluria
2. Model for End-stage Liver Disease (MELD)

English Journal

Hydroxyproline metabolism in a mouse model of Primary Hyperoxaluria Type 3.

Li X1, Knight J1, Todd Lowther W2, Holmes RP3.
Biochimica et biophysica acta.Biochim Biophys Acta.2015 Dec;1852(12):2700-5. doi: 10.1016/j.bbadis.2015.09.016. Epub 2015 Sep 30.
Primary Hyperoxaluria Type 3 is a recently discovered form of this autosomal recessive disease that results from mutations in the gene coding for 4-hydroxy-2-oxoglutarate aldolase (HOGA1). This enzyme is one of the 2 unique enzymes in the hydroxyproline catabolism pathway. Affected individuals have
PMID 26428388

A mutation creating an out-of-frame alternative translation initiation site in the GRHPR 5'UTR causing primary hyperoxaluria type II.

Fu Y1, Rope R1, Fargue S2, Cohen HT3, Holmes RP2, Cohen DM1.
Clinical genetics.Clin Genet.2015 Nov;88(5):494-8. doi: 10.1111/cge.12541. Epub 2014 Dec 26.
Primary hyperoxaluria type II is a recessive genetic disorder caused by mutations in the GRHPR gene. Although several dozen mutations have been described, all affect coding or transcript splicing. A man suspected of having primary hyperoxaluria type II was heterozygous for a novel single-nucleotide
PMID 25410531

Skin manifestations of primary hyperoxaluria: a case report.

Shreberk-Hassidim R1, Zaguri R2, Maly A3, Zlotogorski A1, Ramot Y1.
International journal of dermatology.Int J Dermatol.2015 Nov;54(11):e478-9. doi: 10.1111/ijd.13036. Epub 2015 Jul 30.
PMID 26227278