Hyperoxaluria
Encyclopedia
Hyperoxaluria is an excessive urinary excretion of oxalate
Oxalate
Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either...

. Individuals with hyperoxaluria often have calcium oxalate
Calcium oxalate
Calcium oxalate is a chemical compound that forms needle-shaped crystals, known in plants as raphides. A major constituent of human kidney stones, the chemical is also found in beerstone, a scale that forms on containers used in breweries...

 kidney stone
Kidney stone
A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...

s. Sometimes called Bird's disease, after Golding Bird
Golding Bird
Golding Bird was a British medical doctor and Fellow of the Royal College of Physicians of London. Bird became a great authority on kidney diseases and published a comprehensive paper on urinary deposits...

 who was first to describe the condition.

Causes

Type I (PH1) is associated with AGXT
AGXT
Serine—pyruvate aminotransferase is an enzyme that in humans is encoded by the AGXT gene.-External links:* -Further reading:...

 protein, a key enzyme involved in breakdown of oxalate
Oxalate
Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either...

. PH1 is also an example of a protein mistargeting disease wherein AGXT shows a trafficking defect: instead of being trafficked to peroxisome
Peroxisome
Peroxisomes are organelles found in virtually all eukaryotic cells. They are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, and biosynthesis of plasmalogens, etherphospholipids critical for the normal function of mammalian brains...

s, it is targeted to mitochondria where it is metabolically deficient despite being catalytically active. Type II is associated with GRHPR
GRHPR
Glyoxylate reductase/hydroxypyruvate reductase is an enzyme that in humans is encoded by the GRHPR gene.This gene encodes an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities. The enzyme has widespread tissue expression and has a role in...

.
It is also a complication of jejunoileal bypass
Jejunoileal bypass
Jejunoileal Bypass was a surgical weight loss procedure performed from the 1950s through the 1970s in which all but 30 cm to 45 cm of the small bowel were detached and set to the side....

, or in any patient who has lost much of the ileum
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...

 with an intact colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

. This is due to excessive absorption of oxalate from the colon.

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
Primary hyperoxaluria
Primary hyperoxaluria results in increased excretion of oxalate, with oxalate stones being common. The oxalalate in these common conditions is derived from dietary sources or is secondary to malabsorption...

 was treated with a liver and kidney transplant. Favorable outcome is more likely if a kidney transplant is complemented with a liver transplant given that 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. It is in this sense that we could conditionally understand PH1 as a sort of atavism acting on a molecular level. However, this should be taken as a metaphore with all the caveats of metaphoric thinking applied to science.
Types=
  • Primary hyperoxaluria
  • Enteric hyperoxaluria
  • Idiopathic
    Idiopathic
    Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

     hyperoxaluria
  • Oxalate
    Oxalate
    Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either...

    poisoning

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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