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 o ...

. 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 Golding Bird (9 December 1814 – 27 October 1854) was a British medical doctor and a Fellow of the Royal College of Physicians. He became a great authority on kidney diseases and published a comprehensive paper on urinary deposits in ...

, 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 * Primary (musician), hip hop musician and record producer from South Korea * 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 Serine—pyruvate aminotransferase is an enzyme that in humans is encoded by the ''AGXT'' gene. This gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxifica ...

, a key enzyme involved in

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 pero ...

s, it is targeted to

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

, where it is metabolically deficient despite being catalytically active. Type II is associated with

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. ...

. Secondary hyperoxaluria can occur as a complication of

jejunoileal bypass Jejunoileal bypass (JIB) was a surgical weight-loss procedure performed for the relief of morbid obesity from the 1950s through the 1970s in which all but 30 cm (12 in) to 45 cm (18 in) of the small bowel were detached and set ...

, 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 ma ...

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 rhizo ...

, may also be a cause in rare cases.

Diagnosis

Types

Primary hyperoxaluria Primary hyperoxaluria is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms Primary hyperoxaluria is an ...

* Enteric hyperoxaluria *

Idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...

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 o ...

poisoning

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 is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms Primary hyperoxaluria is an ...

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