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
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 ...
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
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 transplantati ...
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