| Hyperoxaluria | |
|---|---|
| Other names | Bird's disease |
 | |
| Oxalate | |
| Specialty | Endocrinology  |
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.
 | This section is empty. You can help by adding to it. (October 2024) |
Hyperoxaluria can be primary (as a result of a genetic defect) or secondary to another disease process.[ citation needed ]
Type I primary hyperoxaluria (PH1) is associated mutations in the gene encoding AGXT, a key enzyme involved in oxalate metabolism. PH1 is 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]
Secondary hyperoxaluria can occur as a complication of jejunoileal bypass, or in a patient who has lost much of the ileum with an intact colon. In these cases, hyperoxaluria is caused by excessive gastrointestinal oxalate absorption. [2]
Excessive intake of oxalate-containing food, such as rhubarb, may also be a cause in rare cases. [3]
The types are the following:[ citation needed ]
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. A child with primary hyperoxaluria was treated with a liver and kidney transplant. [4] A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver.[ citation needed ]
Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation.[ citation needed ]
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.[ citation needed ]
A peroxisome (IPA:[pɛɜˈɹɒksɪˌsoʊm]) 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 peroxide (H2O2) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the reduction of reactive oxygen species.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes. It is also the most common of the inherited cystic kidney diseases — a group of disorders with related but distinct pathogenesis, characterized by the development of renal cysts and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the liver, seminal vesicles, pancreas, and arachnoid membrane, as well as other abnormalities, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal wall hernias. Over 50% of patients with ADPKD eventually develop end stage kidney disease and require dialysis or kidney transplantation. ADPKD is estimated to affect at least one in every 1000 individuals worldwide, making this disease the most common inherited kidney disorder with a diagnosed prevalence of 1:2000 and incidence of 1:3000-1:8000 in a global scale.
Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.
Oxalate is an anion with the chemical formula C2O2−4. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate, and several esters such as dimethyl oxalate. It is a conjugate base of oxalic acid. At neutral pH in aqueous solution, oxalic acid converts completely to oxalate.
Enoyl-CoA-(∆) isomerase (EC 5.3.3.8, also known as dodecenoyl-CoA- isomerase, 3,2-trans-enoyl-CoA isomerase, ∆3 ,∆2 -enoyl-CoA isomerase, or acetylene-allene isomerase, is an enzyme that catalyzes the conversion of cis- or trans-double bonds of coenzyme A bound fatty acids at gamma-carbon to trans double bonds at beta-carbon as below:
Zellweger syndrome is a rare congenital disorder characterized by the reduction or absence of functional peroxisomes in the cells of an individual. It is one of a family of disorders called Zellweger spectrum disorders which are leukodystrophies. Zellweger syndrome is named after Hans Zellweger (1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder.
Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially.
Peroxisomal disorders represent a class of medical conditions caused by defects in peroxisome functions. This may be due to defects in single enzymes important for peroxisome function or in peroxins, proteins encoded by PEX genes that are critical for normal peroxisome assembly and biogenesis.
Malonyl-CoA decarboxylase, is found in bacteria and humans and has important roles in regulating fatty acid metabolism and food intake, and it is an attractive target for drug discovery. It is an enzyme associated with Malonyl-CoA decarboxylase deficiency. In humans, it is encoded by the MLYCD gene.
Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe the deposition of poorly soluble calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined by progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray. It may be severe enough to cause renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium salts.
In enzymology, a glycerate dehydrogenase (EC 1.1.1.29) is an enzyme that catalyzes the chemical reaction
Palmitoyl-CoA hydrolase (EC 3.1.2.2) is an enzyme in the family of hydrolases that specifically acts on thioester bonds. It catalyzes the hydrolysis of long chain fatty acyl thioesters of acyl carrier protein or coenzyme A to form free fatty acid and the corresponding thiol:
Serine—pyruvate aminotransferase is an enzyme that in humans is encoded by the AGXT gene.
Primary hyperoxaluria is a rare condition, resulting in increased excretion of oxalate, with oxalate stones being common.
Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial is an enzyme that in humans is encoded by the ECH1 gene.
Renal cysts and diabetes syndrome (RCAD), also known as MODY 5 or HNF1B-MODY, is a form of maturity onset diabetes of the young.
Fanconi syndrome or Fanconi's syndrome is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity, or by adverse drug reactions. It results in various small molecules of metabolism being passed into the urine instead of being reabsorbed from the tubular fluid. Fanconi syndrome affects the proximal tubules, namely, the proximal convoluted tubule (PCT), which is the first part of the tubule to process fluid after it is filtered through the glomerulus, and the proximal straight tubule, which leads to the descending limb of loop of Henle.
Zellweger spectrum disorders are a group of rare disorders that create the same disease process. The subdivisions of this spectrum are hyperpipecolic acidemia, infantile Refsum disease, neonatal adrenoleukodystrophy, and Zellweger syndrome. It can also be referred to as peroxisomal biogenesis disorders, Zellweger syndrome spectrum, NALD, cerebrohepatorenal syndrome, and ZSS. It can affect many body organs, including the kidneys, eyes, and hearing. It is named after Hans Zellweger.
Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine, resulting in damage primarily to the liver along with the kidneys and peripheral nerves. The inability of cells to process tyrosine can lead to chronic liver damage ending in liver failure, as well as renal disease and rickets. Symptoms such as poor growth and enlarged liver are associated with the clinical presentation of the disease. If not detected via newborn screening and management not begun before symptoms appear, clinical manifestation of disease occurs typically within the first two years of life. The severity of the disease is correlated with the timing of onset of symptoms, earlier being more severe. If diagnosed through newborn screening prior to clinical manifestation, and well managed with diet and medication, normal growth and development is possible.
Lumasiran, sold under the brand name Oxlumo, is a medication for the treatment of primary hyperoxaluria type 1 (PH1).