NORD gratefully acknowledges John C. Lieske, MD, Professor of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, for assistance in the preparation of this report.
Primary hyperoxaluria (PH) is a group of rare genetic metabolic disorders that are characterized by the accumulation of a substance known as oxalate in the kidneys and other organ systems of the body. Affected individuals lack functional levels of a specific enzyme that normally prevents the accumulation of oxalate. There are three main types of PH – PH types I, II, and III – differentiated by the specific enzyme that is deficient. In the kidneys, excess oxalate binds with calcium to form a hard compound (calcium oxalate) that is the main component of kidney and urinary stones. Common symptoms include the formation of stones throughout the urinary tract (urolithiasis) and kidneys (nephrolithiasis) and progressively increased levels of calcium in the kidneys (nephrocalcinosis). Chronic, recurrent stone formation and the accumulation of calcium oxalate in kidney tissue can cause chronic kidney disease, which can ultimately progress to kidney failure. Eventually, kidney function can deteriorate to the point where oxalate begins to accumulate in other organ systems. Overall, the symptoms and severity of PH may vary greatly from one person to another. Chronic kidney disease and kidney failure may already be present when a diagnosis is first made. PH is a treatable disorder and complications may be minimized with early recognition and prompt treatment.
PH is inherited in an autosomal recessive pattern. The genetic mutations that cause PH control the production of different enzymes found primarily in the liver in PH type I and PH type II, and in the kidney and liver in PH type III. The significance of the enzyme found in the kidney remains to be determined.
PH has characteristic or “core” symptoms, but some aspects of these disorders are still not fully understood. Several factors including the small number of identified cases (especially with PH types II and III), the lack of large clinical studies, and multiple genes influencing the disorders prevent physicians from developing a complete picture of associated symptoms and prognosis. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.
The age of onset, progression, severity and specific symptoms that develop can vary greatly from one person to another, even in individuals with the same subtype and even among members of the same family. Some individuals may have mild cases that go undiagnosed well into adulthood; others may develop severe complications during infancy. In some individuals kidney involvement may progress slowly, while in others it may progress rapidly.
PRIMARY HYPEROXALURIA TYPE I
PH type I is the most severe and most common of the three types. It is estimated to account for 70 to 80% of all diagnosed PH patients. The severe infantile form is associated with the failure to gain weight and grow at the expected rate for age and gender (failure to thrive), widespread calcium oxalate crystal deposits in the kidneys, and/or kidney stones or stones elsewhere in the urinary tract such as the bladder or urethra. Kidney and urinary stones can cause a variety of symptoms including blood in the urine (hematuria), painful urination (dysuria), the urge to urinate often, abdominal pain (renal colic), blockage of the urinary tract, and repeated urinary tract infections. PH type I often causes progressive kidney damage and kidney failure.
When PH type I develops during childhood or adolescence, the disorder is usually characterized by recurrent stones in the kidney or elsewhere in the urinary tract such as the bladder or urethra. Younger children may experience difficulty controlling their urine and/or bedwetting (enuresis). Progressive kidney damage leading to kidney failure may develop.
Some individuals are not diagnosed with PH type I until adulthood and only experience occasional or recurrent episodes of kidney stones. In some cases, these individuals may develop kidney failure due to the obstruction of the kidneys by stones. Although usually described as a mild form of the disorder, approximately 20-50% of individuals diagnosed with PH type I in adulthood have advanced kidney disease or even kidney failure. In rare cases, a diagnosis may not be made until a kidney transplant rapidly fails due to recurrent disease. If kidney function declines in a person with PH, oxalate begins to accumulate in other organ systems of the body particularly bone, skin, retinas in the eyes, the middle layer of the wall of the heart (myocardium), various blood vessels, and the central nervous system. This is known as systemic oxalosis and occurs in patients with PH once oxalate levels in the blood become very high and kidney disease is advanced. Depending upon the organ system involved, affected individuals can develop additional symptoms including bone pain; multiple fractures; abnormal hardening and density of bone (osteosclerosis); anemia that is difficult to treat (erythropoietin-resistant anemia); degeneration of the cranial nerve that transmits light signals to the brain (optic atrophy) and disease of the retina (retinopathy); root resorption, pulp exposure, tooth mobility, and dental pain; damage to the nerves outside of the central nervous system (peripheral neuropathy); heart block, irregular heartbeats (arrhythmias), inflammation of the myocardium (myocarditis), and cardioembolic stroke; narrowing of a blood vessel due to spasms of the vessel (vasospasm); joint disease (arthropathy); enlargement of the liver and/or spleen (hepatosplenomegaly); and purplish mottling of the skin (livedo reticularis); tissue death (necrosis) on the hands and feet (peripheral gangrene); and a skin rash caused by calcium deposits in the skin (calcinosis cutis metastatica).
PRIMARY HYPEROXALURIA TYPE II
PH type II usually presents during childhood and the disorder is more likely to have a milder presentation than PH type I. It is thought to account for approximately 10% of PH cases. Affected individuals can develop similar symptoms and have similar oxalate levels to those seen in individuals with PH type I but usually develop kidney and urinary stones less often. PH type II can eventually progress to cause kidney failure, although this often happens later than it does in PH type I. When kidney function declines, the accumulation of oxalate in other organ systems of the body as described above may also occur.
PRIMARY HYPEROXALURIA TYPE III
Because so few cases of PH type III have been identified, it is difficult to make definite statements about disease severity and progression, but it is estimated to be at least as common as PH type II, accounting for approximately 10% of cases. The disorder is considered milder than PH types I or II. Affected individuals may have no symptoms, or may only experience kidney stone formation. Symptoms due to frequent kidney stones can begin at an early age, but overall decline in kidney function is slowest with type III, and oxalate levels are lowest. Typical signs and symptoms include stone formation in the urinary tract in the first decade of life that can persist throughout adulthood. Nephrocalcinosis and chronic kidney disease are uncommon. Advanced kidney disease has rarely been reported.
UNCLASSIFIED PRIMARY HYPEROXALURIA
In some cases, patients present with signs and symptoms typical of PH but lack any identifiable mutation in the known associated genes AGXT, GRHPR, or HOGA1. They are currently diagnosed with unclassified PH, leading researchers to suspect there are other yet to be identified genetic mutations that can cause PH.
PH type I is caused by changes (mutations) in the AGXT gene. PH type II is caused by mutations in the GRHPR gene. PH type III is caused by mutations in the HOGA1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.
The AGXT gene creates (encodes) the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. The GRHPR gene encodes the enzyme glyoxylate reductase-hydroxypyruvate reductase. Mutations in either of these genes lead to deficient levels of the corresponding enzyme. These enzymes play a role in regulating the production of oxalate. Deficient levels of these enzymes ultimately lead to the overproduction of oxalate in the body. The HOGA1 gene encodes liver-specific mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase. The exact role this enzyme plays in the production of oxalate is not fully understood. Thus researchers are not sure why a mutation in this gene leads to the overproduction of oxalate.
Oxalate is a chemical found in the body. It is a dicarboxylic acid that is a normal end product of metabolism. It cannot be further metabolized. Metabolism refers to the various normal chemical processes that occur within a living organism. Most oxalate in the body is produced in the liver, although some may come from certain foods. Oxalate has no known role in the body and is considered a waste product of metabolism. Normally, most oxalate in the body (in the form of calcium salt) is removed from the body (excreted) through the kidneys. In individuals with PH, deficiency of the abovementioned enzymes results in overproduction of oxalate by the liver, which causes increased oxalate excretion by the kidneys. Some of the excess oxalate begins to accumulate in kidney tissue in the form of calcium oxalate crystals. This abnormal accumulation causes progressive damage to the kidneys and, if untreated, may ultimately cause kidney failure.
A second phase of PH occurs when the glomerular filtration rate (GFR) of the kidneys drops far enough. The GFR is the flow rate of filtered fluid through the kidneys. When the GFR of a PH patient drops low enough, the kidneys are no longer able to handle the excess amounts of oxalate and the chemical begins to accumulate in other tissues of the body causing a wide variety of symptoms.
The progression and severity of PH is highly variable. This may be due, in part, to specific mutations in genes corresponding with specific symptoms or disease progression. The association of a specific mutation in a gene to specific symptoms is known as genotype-phenotype correlation. Some individuals with specific AGXT mutations that cause PH type I (for example the mutations called p.G170R and p.F152I) respond to treatment with vitamin B6 (pyridoxine) while patients with other AGXT mutations do not. To date more than 170 different mutations in the AGXT gene have been identified that cause PH type I. Certain genetic mutations within each of the three types of PH are also predictive of which patients are less likely to develop kidney failure. Some research suggests that specific mutations of the AGXT gene, such as p.G170R, are associated with milder disease or later onset kidney failure. No specific genotype-phenotype correlation has been established yet in PH type II and III. There is more variation between genetic mutations for PH type I and II compared with PH type III.
Because of variability in symptoms and disease progression, recent research has focused on identifying factors that help predict which patients will progress to kidney failure before it occurs. Factors associated with an increased likelihood of eventual progression to kidney failure include diagnosis of PH type I, older age when diagnosed with PH, higher urine oxalate levels, and low GFR at diagnosis. Urine oxalate levels are considered the greatest predictor among these. Higher urinary oxalate is associated with the development of nephrocalcinosis, which lead to chronic kidney damage through repetitive inflammation and permanent tissue changes that alter the function of the kidneys.
It is likely that other factors contribute to disease variability in PH. These may include environmental factors and additional genetic factors (i.e., other genes that modify the disease course). However, no specific environmental or additional genetic factors have yet been identified.
PH is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two parents that are each carriers to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier is 50% with each pregnancy. The chance for a child to receive working genes from both parents and thus be unaffected is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. PH appears to be more common in countries in which consanguineous marriage is common.
PH affects males and females in equal numbers. The exact incidence and prevalence of these disorders is unknown. Because some cases go undiagnosed or misdiagnosed, determining the true frequency of these conditions in the general population is difficult. Molecular genetic testing of young patients with recurring kidney stone formation can aid in diagnosis. However, some patients with common symptoms of PH are not found to have the known genetic mutations linked to PH, which likely underestimates the true number of people with PH. PH type I is the most common form. One estimate places the prevalence of PH type I at 1-3 cases per 1,000,000 people in the general population with fewer than 1,000 individuals with PH in the United States and the incidence at 1 case per 120,000 live births per year in Europe. PH is thought to be approximately 2.5 times more common in European Americans than African Americans.
A diagnosis of PH is based upon identification of characteristic symptoms (e.g. chronic stone formation), a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Children with nephrocalcinosis or kidney stones should be screened for PH. PH may be suspected in individuals with a history of recurrent kidney stones and/or nephrocalcinosis. Because these conditions are rare, there may a delay from symptom onset to diagnosis.
Investigation for PH includes measuring urine and plasma oxalate levels, ruling out other causes of high oxalate levels (dietary or enteric hyperoxaluria), molecular genetic testing for mutations known to be associated with PH and detecting the presence of kidney stones and examining their composition.
Clinical Testing and Workup
Chemical analysis of urine samples may reveal elevated levels of oxalate, although this is a fluctuating and variable finding. Glycolate (glycolic acid) in PH type I and L-glycerate in PH type II may also be elevated in urine samples, but are nonspecific (i.e., they may be elevated for reasons other than PH). In some cases of PH type III, urinary calcium levels are abnormally high. Most individuals with PH type III have elevated levels of 4-hydroxyglutamate in the urine and blood, which could potentially be incorporated into multiple-analyte panels for newborn screening for inborn errors of metabolism. Blood tests can reveal high plasma oxalate concentration in individuals with PH who have chronic kidney disease. Otherwise, plasma oxalate levels are often normal or only mildly increased because the kidneys are able to excrete enough oxalate to keep plasma levels in the normal range.
X-ray examinations can reveal the presence of kidney stones or calcium oxalate deposits in tissue. Computed tomography (CT) scanning, a specialized imaging technique, uses a computer and x-rays to create a film showing cross-sectional images of certain tissue structures such as kidney tissue. CT or MRI can detect the severity of systemic oxalosis by imaging the retina, heart, and bone in greater detail.
A biopsy of affected kidney tissue can also reveal the abnormal accumulation of oxalate. A biopsy involves the surgical removal and microscopic examination of a piece of affected tissue. Previously, a liver biopsy was used to obtain a tissue sample to conduct an enzyme assay as a way to diagnose primary hyperoxaluria. An enzyme assay is a test that measures the activity of a specific enzyme. Such an assay can demonstrate low levels of the specific enzymes that are associated with the specific forms of PH. Today the need for liver biopsy has been greatly decreased due to the increasingly lower cost and improved sensitivity of modern molecular genetic testing.
Examination of kidney stones can provide evidence to support the possibility of PH in comparison to other causes of kidney stone disease. The stones associated with PH tend to consist of more than 95% calcium oxalate monohydrate (whewellite), are usually pale-colored and may come in varying sizes, shapes and appearances (non-homogeneous). Although idiopathic stone formers can also produce calcium oxalate monohydrate stones, they also often contain some amount of calcium oxalate dihydrate and or calcium phosphate.
Molecular genetic testing for mutations in the 3 specific genes known to cause PH confirms the diagnosis of PH.
The treatment of PH is directed toward the specific symptoms that are present in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who assess and treat problems of the kidneys (nephrologists), specialists who assess and treat problems of the liver (hepatologists), specialists who assess and treat problems of the urinary tract (urologists), dieticians, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling is recommended to help families understand the genetics and natural history of PH and to provide psychosocial support.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; specific subtype; responsiveness to pyridoxine; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.
Prompt diagnosis and early therapy are essential to slowing progression of the disorder and preserving kidney function as long as possible. Early conservative methods can reduce or prevent kidney stone formation. Adequate fluid intake can help to prevent the formation of kidney stones. Drinking large amounts of water dilutes the oxalate that ends up in the urine and reduces the risk of its crystallization with calcium. Some infants and small children may require a procedure known as gastrostomy to ensure proper fluid intake and dilution of the urine. With this procedure, a thin tube is placed into the stomach via a small incision in the abdomen, allowing for the direct intake of food, fluids, and/or medicine.
Certain medications may be used to treat individuals with PH including potassium citrate, thiazides, magnesium, or orthophosphates. These medications in combination with water intake can further reduce the risk of calcium and oxalate crystallization but often do not entirely prevent stone formation or kidney failure.
Some individuals with PH type I (but not with other forms of PH) respond to dietary supplementation with pyridoxine, also known as vitamin B6. In such cases, pyridoxine supplementation leads to a reduction in oxalate levels. Not all individuals with PH type I respond to pyridoxine therapy. Pyridoxine is a metabolic precursor to a co-factor necessary for function of AGT, the protein affected in PH type I. Certain PH type I mutations are known to predict a good response to pyridoxine. Patients with one copy of these mutations are typically partially responsive, while those with two copies are completely responsive.
For individuals who experience repeated stone formation, sometimes referred to as a high stone burden, a procedure that uses shock waves (lithotripsy) to break up stones in the urinary tract and kidneys may be recommended. The most common type, extracorporeal shock wave lithotripsy, is usually not recommended for individuals with PH because the stones are hard and don’t easily break up by this method. Instead, minimally invasive methods such as ureteroscopic laser lithotripsy may be recommended. During this procedure, a small tube or scope is inserted into the bladder and the ureter (the tube through which urine passes from the kidneys to the bladder). If a stone is small, the scope can be used to remove the stone whole. If the stone is too large, the stone will be broken apart with a laser. The stone fragments are then removed.
Some physicians recommend dietary restriction of foods high in oxalate as a precautionary measure. Although the amount of oxalate in the diet is usually small in comparison to that produced by the liver, however avoiding a high oxalate intake makes good common sense. Foods high in oxalate include chocolate, rhubarb, and starfruit. Vitamin D and vitamin C should be avoided in large doses. Affected individuals should also avoid becoming dehydrated as maintaining dilute urine is extremely important in preventing stone formation.
If kidney function declines over time, or in cases where an individual is first diagnosed with PH after the development of advanced kidney disease or kidney failure, additional specific treatments will be required. It is critically important that PH patients that developed kidney failure promptly diagnosed because the treatment of kidney failure differs compared to other causes of kidney failure. Specific treatments may include intensive dialysis, a liver transplant, a combined liver-kidney transplant or a kidney transplant. The specific therapy used will depend upon an individual’s specific case and requirements.
Dialysis may be used to treat individuals with PH but is not considered an effective long-term solution. Dialysis is a procedure in which a machine is used to perform the kidney’s basic functions of fluid and waste removal. Dialysis can help clear oxalate and other toxins from the body. However, dialysis (both conventional hemodialysis and peritoneal dialysis) fails to adequately remove enough oxalate to prevent oxalate accumulation. Thus, patients often require more frequent dialysis session than typical kidney failure patients (often 5 or 6 times per week as opposed to the usual 3 times per week). In addition, peritoneal dialysis is not very effective for removing oxalate and many home hemodialysis systems are also not particularly effective for oxalate removal. However, dialysis less often be used in specific situations or until a kidney and/or liver transplant can be performed. Unfortunately, kidney transplant alone is usually not an effective means of treatment either, since the high oxalate levels excreted into the urine can damage the new transplanted kidney.
For some individuals, a liver transplantation may be recommended. Since the liver is the only organ that produces the enzyme that is deficient in PH type I, a new liver will restore production of the missing enzyme. A liver transplantation may be considered in individuals without advanced kidney disease (preemptive liver transplantation), but its use as an isolated procedure early in the course of the renal decline is controversial because the benefits must be weighed against a relatively high immediate post-operative mortality. Life-long immunosuppression is also required after transplantation.
In some cases of PH type I, affected individuals may be recommended for a combined liver-kidney transplant if the kidneys are already too damaged (i.e. stage 4 chronic kidney disease). In other cases (stage 5 chronic kidney disease), sequential transplantation, the liver followed by the kidney, may be recommended.
An isolated kidney transplant may also be performed in individuals with PH type I, but has generally been replaced by preemptive liver transplantation or combined liver-kidney transplantation. Since the underlying defect in PH type I is in the liver, an isolated kidney transplant has a high level of recurrence of kidney disease.
PH type II may be treated by isolated kidney transplantation, which has been varyingly successful. Although the enzyme that is deficient in PH type II is widespread throughout tissues of the body, it appears that the majority of oxalate is produced in the liver much like PH type I. Consequently, a combined liver-kidney transplant has been reported in a few cases to date suggesting this strategy may also be effective in PH type II.
At this time, only one case of renal failure has been reported in PH type III, so transplants are not typically needed for this type.
Oxlumo (lumasiran) is the first viable drug alternative to transplantation for PH type I to be approved by the U.S. Food and Drug Administration (FDA). Oxlumo successfully lowers urinary oxalate levels. It is a type of gene therapy known as RNA interference that silences defective genes by disrupting protein formation necessary for gene expression. Oxlumo does not target the defective AGT enzyme itself but instead targets glycolate oxidase (GO), a normally-functioning enzyme that contributes to oxalate production. By reducing the amount of GO, Oxlumo compensates for the overproduction of oxalate that results from the defective genes in PH type I.
Another RNA interference therapy under clinical investigation similar to lumasiran is nedosiran. It disrupts the function of the enzyme lactate dehydrogenase type a (LDHa) to lower oxalate levels. LDHa is only expressed in the liver, and blocking it could potentially decrease oxalate production in all 3 types of PH.
Other gene therapies are also being studied for patients with PH. In gene therapy, the defective gene present in a patient is either turned off and no longer able to function, as is the case with RNA interference, or is replaced with a normal gene to enable the production of the active enzyme and prevent the development and progression of the disease. The latter is known as gene replacement therapy and is the form of therapy theoretically most likely to lead to a “cure” because it involves the permanent transfer of the normal gene, which is then able to produce active enzyme at all sites of disease. However, at this time, there remain some technical difficulties to resolve before this type of gene therapy can be advocated as a viable alternative approach.
Similar to gene therapy is cell therapy, in which liver cells (hepatocytes) are repopulated into the liver of an individual with PH type I. If successful, these normal or genetically-modified liver cells would restore the proper activity of the enzyme alanine-glyoxylate aminotransferase. However, as with gene therapy, significant technical difficulties remain to be resolved.
The AGT enzyme associated with PH type I may, in some cases, be capable of at least partial enzymatic activity but is misshapen (misfolded), becoming trapped within the cell, or is broken down by cellular quality control processes. Researchers are studying drugs that may be able to stabilize and guide (chaperone) the defective AGT enzyme to the proper place. Researchers believe that these pharmacological chaperones can bind with receptor proteins preserving enough of the natural shape and function of the proteins that they do not become trapped within the cells or targeted by the quality control processes, and can travel to their proper destination and perform their intended function. More research is necessary to determine the long-term safety and effectiveness of these potential treatments for individuals with PH.
Probiotics, which are foods or dietary supplements that contain live bacteria that replace or complement beneficial bacteria normally found in the gastrointestinal tract, may have a role in decreasing absorption of oxalate form the intestine. Certain probiotics such as Oxalobacter formigenes break down oxalate in the intestine, and may secrete a factor that stimulates excretion of oxalate into the intestine from the blood. The net effect is to reduce oxalate in the blood that must be excreted by the kidneys. Other bacteria or combinations of bacteria may have similar effects. However, no clinical studies today have demonstrated that this approach can work to treat patients with primary hyperoxaluria.
A registry for hereditary calcium stone disorders, including primary hyperoxaluria, has been set up by the Oxalosis and Hyperoxaluria Foundation (OHF) and Rare Kidney Stone Consortium (RKSC) and is currently housed at the Mayo Clinic. A registry is a special database that contains information about individuals with a specific disorder or group of conditions. The collection of data about rare disorders enables researchers to increase the understanding of such disorders, expand the search for treatments, and accelerate clinical trials into specific treatment options.
For more information, contact:
Rare Kidney Stone Consortium
Email: [email protected]
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Hu B, Zhong L, Weng Y, et al. Therapeutic siRNA: state of the art. Signal Transduct Target Ther. 2020:5:101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305320/
Milliner D, McGregor T, Thompson A, et al. Endpoints for clinical trials in primary hyperoxaluria. Clin J Am Soc Nephrol. 2020:15(7):1056-1065. https://pubmed.ncbi.nlm.nih.gov/32165440/
Zhao F, Bergstralh E, Mehta R, et al. Predictors of incident ESRD among patients with primary hyperoxaluria presenting prior to kidney failure. Clin J Am Soc Nephrol. 2016:11(1):119-26. https://pubmed.ncbi.nlm.nih.gov/26656319/
Hopp K, Cogal A, Bergstralh E, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J. Am. Soc. Nephrol. 2015:26:2559-2570. https://pubmed.ncbi.nlm.nih.gov/25644115/
Mandrile G, van Woerden CS, Berchialla P, et al. Data from a large European study indicate that the outcome of primary hyperoxaluria type 1 correlates with AGXT mutation type. Kidney Int. 2014; [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/24988064
Lorenz EC, Lieske JC, Seide BM, et al. Sustained pyridoxine response in primary hyperoxaluria type 1 recipients of kidney alone transplant. Am J Transplant. 2014;14:1433-1438. http://www.ncbi.nlm.nih.gov/pubmed/24797341
Pitt JJ, Willis F, Tzanakos N, Belostotsky R, Frishberg Y. 4-hydroxyglutamate is a biomarker for primary hyperoxaluria type 3. JIMD. 2014; [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/24563386
Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013;369:649-658. http://www.ncbi.nlm.nih.gov/pubmed/23944302
Lorenz EC, Michet CJ, Milliner DS, Lieske JC. Update on oxalate crystal disease. Cur Rheumatol Rep. 2013;15:340. http://www.ncbi.nlm.nih.gov/pubmed/23666469
Beck BB, Baasner A, Beuscher A, et al. Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies. Eur J Hum Genet. 2013;21:162-172. http://www.ncbi.nlm.nih.gov/pubmed/22781098
Jacob DE, Grohe B, Gebner M, Beck BB, Hoppe B. Kidney stones in primary hyperoxaluria: new lessons learnt. PLoS. 2013;8:e70617. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734250/
Van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort. Nephrol Dial Transplant. 2012;27:3855-3862. http://www.ncbi.nlm.nih.gov/pubmed/22844106
Cochat P, Sulton SA, Acquaviva C, et al. Primary hyperoxaluria type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant. 2012;27:1729-1736. http://www.ncbi.nlm.nih.gov/pubmed/22547750
Harambat J, Fargue S, Bacchetta J, Acquaviva C, Cocha P. Primary hyperoxaluria. Int J Nephrol. 2011;2011:864580. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124893/
Mookadam F, Smith T, Jiamspring P, et al. Cardiac abnormalities in primary hyperoxaluria. Circ J. 2010;74:2403-2409. http://www.ncbi.nlm.nih.gov/pubmed/20921818
Belostosky R, Seboun E, Idelson GH, et al. Mutations in DHDPSL are responsible for primary hyperoxaluria type III. Am J Hum Genet. 2010;87:392-399. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933339/
Beck BB, Hoppe B. Is there a genotype-phenotype correlation in primary hyperoxaluria type 1? Kidney Int. 2006;70:984-986. http://www.ncbi.nlm.nih.gov/pubmed/16957746
Hoppe B, Beck B, Gatter N, et al. Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1. Kidney Int. 2006;70:1305-1311. http://www.ncbi.nlm.nih.gov/pubmed/16850020
Milliner DS, Harris PC, Cogal AG, et al. Primary Hyperoxaluria Type 1. 2002 Jun 19 [Updated 2017 Nov 30]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1283/ Accessed November 30, 2020.
Rumsby G, Hulton SA. Primary Hyperoxaluria Type 2. 2008 Dec 2 [Updated 2017 Dec 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2692/ Accessed November 30, 2020.
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