Hyperoxaluria is an excessive urinary excretion of
oxalate
Oxalate (IUPAC: ethanedioate) is an anion with the formula C2O42−. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (Na2C2O4), and several esters such as dimethyl ...
. Individuals with hyperoxaluria often have
calcium oxalate
Calcium oxalate (in archaic terminology, oxalate of lime) is a calcium salt of oxalic acid with the chemical formula . It forms hydrates , where ''n'' varies from 1 to 3. Anhydrous and all hydrated forms are colorless or white. The monohydrate ...
kidney stone
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
s. It is sometimes called Bird's disease, after
Golding Bird, who first described the condition.
Causes
Hyperoxaluria can be
primary
Primary or primaries may refer to:
Arts, entertainment, and media Music Groups and labels
* Primary (band), from Australia
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* Primary Music, Israeli record label
Works
...
(as a result of a genetic defect) or secondary to another disease process.
Type I primary hyperoxaluria (PH1) is associated mutations in the gene encoding
AGXT, a key enzyme involved in
oxalate
Oxalate (IUPAC: ethanedioate) is an anion with the formula C2O42−. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (Na2C2O4), and several esters such as dimethyl ...
metabolism. PH1 is an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect. Instead of being trafficked to
peroxisome
A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen pe ...
s, it is targeted to
mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
, where it is metabolically deficient despite being catalytically active. Type II is associated with
GRHPR.
Secondary hyperoxaluria can occur as a complication of
jejunoileal bypass, or in a patient who has lost much of the
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 m ...
with an intact
colon. In these cases, hyperoxaluria is caused by excessive gastrointestinal oxalate absorption.
Excessive intake of oxalate-containing food, such as
rhubarb
Rhubarb is the fleshy, edible stalks ( petioles) of species and hybrids (culinary rhubarb) of '' Rheum'' in the family Polygonaceae, which are cooked and used for food. The whole plant – a herbaceous perennial growing from short, thick rhi ...
, may also be a cause in rare cases.
Diagnosis
Types
*
Primary hyperoxaluria
* Enteric hyperoxaluria
*
Idiopathic
An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...
hyperoxaluria
*
Oxalate
Oxalate (IUPAC: ethanedioate) is an anion with the formula C2O42−. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (Na2C2O4), and several esters such as dimethyl ...
poisoning
Treatment
The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e.
kidney transplantation
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantat ...
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.
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.
References
External links
GeneReviews/NIH/NCBI/UW entry on Primary Hyperoxaluria Type 1
{{DEFAULTSORT:Hyperoxaluria
Abnormal clinical and laboratory findings for urine
Inborn errors of carbohydrate metabolism