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At least 19 recordsLinked to original sources
PubMed1990

Ocular findings in primary hyperoxaluria.

Primary hyperoxaluria (primary oxalosis) is a rare autosomal recessive inborn error of glyoxylate metabolism that causes widespread calcium oxalate crystal deposition in diverse tissues. Because others have reported only occasional ocular involvement, we reviewed the ophthalmologic findings in our 24 patients with primary hyperoxaluria to document its funduscopic variability and to determine its visual prognosis and its possible systemic significance. Eight (30%) of our 24 patients with primary hyperoxaluria exhibited a bilaterally symmetrical retinopathy. The abnormalities were predominantly confined to the posterior pole and ranged from many small (100- to 200-microns) subretinal black ringlets to single large (2- to 3-disc diameter) geographic lesions. In 3 of the 8 patients with oxalate retinopathy, diffuse optic disc pallor was evident. Five patients with both normal-appearing optic discs and oxalate retinopathy had relatively good visual acuities. The maculopathy of primary hyperoxaluria caused mild visual impairment while optic nerve dysfunction associated with this disease appeared to be much visually debilitating. Also, the presence of oxalate maculopathy was associated with a more severe systemic course for the disease.

Acute Kidney Injury↗
PubMedDate not supplied

Unusual morphology of calcium oxalate calculi in primary hyperoxaluria.

Primary hyperoxaluria (PH) is a severe inherited disease induced by an enzymatic deficiency responsible for high endogenous production of oxalate. Oxalate ions are excreted by the kidney where they can form an insoluble salt with calcium ions, thus inducing urinary stones, crystal deposition in the tubular lumen and renal parenchyma leading to nephrocalcinosis and renal failure. Eighty-seven calculi from 63 PH patients with primary hyperoxaluria were analyzed and compared to 24,130 calculi from unselected consecutive stone formers referred to our laboratory between January 1977 and December 1996. All stones were analyzed according to a protocol including morphological examination of both surface and cross-section, and sequential infrared identification of the crystalline phases. A typical aspect of both surface and section corresponding to morphological type Ic according to our proposed classification (Daudon et al. Scanning Microsc 1993, 7:1081-1106) was observed in all patients but two whereas only two type Ic stones were observed among patients without primary hyperoxaluria. The latter two patients suffered from severe inflammatory bowel disease and developed heavy hyperoxaluria following extensive ileal resection. We conclude that evidence of type Ic morphology is a simple, cheap and fast tool to detect diseases with heavy hyperoxaluria such as primary hyperoxaluria.

Adult↗
PubMed1996

[Primary hyperoxaluria].

Primary hyperoxaluria is a rare hereditary disease. Two types have been identified. Type 1 is due to the deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase/serine: pyruvate amino-transferase whereas, in type 2, the deficiency concerns the glyoxylate reductase/D-glycerate dehydrogenase, a cytosolic enzyme present in the leucocytes and hepatocytes. In the elapsed decade, important progress in molecular biology led to the introduction of new strategies in the diagnosis and treatment of type 1 primary hyperoxaluria. However, the greater rarity of type 2 has so far prevented similar development. The present review recalls the normal metabolism of oxalic acid, details its deviations and their clinical consequences, and describes the methods of diagnosis and treatment to be presently recommended in primary hyperoxaluria.

Biopsy↗
PubMed1997

Extraction of glyceric and glycolic acids from urine with tetrahydrofuran: utility in detection of primary hyperoxaluria.

Primary hyperoxaluria (PH) is an autosomal recessive metabolic abnormality characterized by excessive oxalate excretion leading to nephrocalcinosis and progressive renal dysfunction. Type I primary hyperoxaluria (PH I) results from a deficiency of alanine:glyoxylate aminotransferase, whereas type II disease has been traced to a deficiency of D-glycerate dehydrogenase. The two syndromes are often distinguished on the basis of organic acids that are coexcreted with oxalate: glycolate and L-glycerate in type I and type II disease, respectively. Routine organic acid analysis with diethyl ether extraction followed by gas chromatographic analysis failed to detect normal and increased concentrations of these diagnostic metabolites. Subsequent extraction of urine with tetrahydrofuran (THF), however, extracted 75% of added glycerate, 42% of added glycolate, and 75% of added ethylphosphonic acid (internal calibrator). THF extraction was analytically sensitive enough to allow determination of normal excretion of glycolate (14-72 micrograms/mg creatinine) and glycerate (0-5 years, 12-177 micrograms/mg creatinine and > 5 years, 19-115 micrograms/mg creatinine). Four of five patients with PH I and both patients with type II disease were correctly identified. Thus, THF extraction is a convenient adjunct to routine organic acid analysis and facilitates the detection of PH.

Adolescent↗
PubMed1992

Oxalate balance studies in patients on hemodialysis for type I primary hyperoxaluria.

Primary hyperoxaluria type I (PH1) always leads to end-stage renal failure (ESRF) due to deposition of calcium oxalate in the kidney. Regular dialysis therapy (RDT) can not overcome the excess production of oxalate, hence, systemic oxalate deposition occurs. The extent of tissue deposition and the rate at which oxalate accumulates influence the quality of life and survival of the patients. Therefore, an estimate of the oxalate balance needs to be made for patients on RDT. In this study, we suggest a simple model by which some of the main parameters of oxalate turnover can be assessed without using radioactive materials. Levels of oxalate, glycolate, and urea, and degrees of calcium oxalate saturation, were assessed on plasma ultrafiltrates from two patients with PH1, sampled before, at the end of a dialysis session, and over the entire interdialytic interval. In patients with PH1, oxalate increased linearly during the early phases and then the curve flattened at a concentration corresponding to approximately threefold saturation. The initial phase of the relationship was used to estimate generation rate of oxalate. The delayed phase was ascribed to the deposition of newly generated oxalate out of its miscible pool. Conversely, the relationship for glycolate and urea remained linear. This was also different from the values obtained in four patients with oxalosis-unrelated ESRF, whose oxalate levels increased linearly over the entire interdialytic interval. In the two patients with PH1, the overall oxalate generation was assessed at 4 to 7 mmol/d. The difference between generation and dialysis removal indicated that tissue deposition was greater than 50 mumol/kg body weight/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Feasibility of hepatocyte transplantation-based therapies for primary hyperoxalurias.

Primary hyperoxalurias (PHs) are diseases caused by overproduction of oxalate by hepatocytes. Most patients with PHs develop nephrocalcinosis and renal failure. Combined liver-kidney transplantation is often used as a definitive treatment of PHs, but because of a large body oxalate load at the time of transplantation, the procedure is not always successful. Because all hepatocytes overproduce oxalate, partial liver replacement procedures, such as auxiliary transplantation of a liver lobe or hepatocyte transplantation are not expected to be useful in this disorder. In this paper we describe novel techniques, based on preparative hepatic irradiation and stimulation of hepatocyte mitosis, through loss of liver mass or administration of hepatic growth factor, which permit transplanted wild-type hepatocytes to massively repopulate the liver, replacing up to 90% of the hepatocytes in recipient mouse livers. Application of this procedure in a recently developed Agxt-gene-deleted mouse model of PH1 resulted in marked amelioration of hyperoxaluria. We propose that further refinement of the different components of this procedure may permit early cell-based therapies of PHs, thereby preventing renal failure and its complications.

Animals↗
PubMed2001

AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder that is caused by a deficiency of alanine: glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical, and enzymological data to evaluate genotype-phenotype correlation. Twenty-three unrelated, Italian PH1 patients were studied, 20 of which were grouped according to severe form of PH1 (group A), adult form (group B), and mild to moderate decrease in renal function (group C). All 23 patients were analyzed by using the single-strand conformation polymorphism technique followed by the sequencing of the 11 AGXT exons. Relevant chemistries, including plasma, urine and dialyzate oxalate and glycolate assays, liver AGT activity, and pyridoxine responsiveness, were performed. Both mutant alleles were found in 21 out of 23 patients, and 13 different mutations were recognized in exons 1, 2, 4, and 10. Normalized AGT activity was lower in the severe form than in the adult form (P < 0.05). Double heterozygous patients presented a lower age at the onset of the disease (P = 0.025), and they were more frequent in group A (75%) than in the group B (14%; P = 0.0406). The T444C mutation was more frequent in the severe form (P < 0.05), and the opposite was observed for G630A (P < 0.05). G630A mutation homozygotes had a higher AGT residual activity (P = 0.00001). This study confirms the allelic heterogeneity of the AGXT, which could to some extent be responsible for the phenotypic heterogeneity in PH1.

Adolescent↗
PubMed2002

Renal graft failure due to type 1 primary hyperoxaluria.

Primary hyperoxaluria type 1 (PH1) usually presents with recurrent urolithiasis, nephrocalcinosis and progressive renal failure at a relatively young age. This report describes a patient who, due to the late onset of end-stage renal disease, had been diagnosed with PH1 only after failure of his second kidney graft. Retrospectively, his vascular problems, skeletal abnormalities and cardiac arrhythmias fit the picture of severe systemic oxalosis. Possible therapeutic options are discussed.

Diagnosis, Differential↗
PubMed1989

[Primary hyperoxaluria].

Primary hyperoxaluria is a recessive hereditary disturbance of glyoxylate metabolism caused by deficiency of the liver enzyme, alanine glyoxylate transaminase. The main symptoms are recurrent renal stones, nephrocalcinosis and renal failure. In the advanced state, the disease is frequently complicated by osseous disease, vascular insufficiency and cardiac arrhytmias caused by deposits of calcium oxalate in the tissue. The prognosis is poor. No specific medical treatment exists. Dialysis is not effective and the results of renal transplantation is poor. Combined liver and renal transplantation correct the metabolic defect and the excretion of oxalate is normalised. Combined transplantation must be regarded as the optimal treatment of renal failure caused by PHO. The transplantation should be undertaken preferably before the creatinine clearance falls below 10-20 ml/min in order to avoid tissue deposits of calcium oxalate and excessive urinary excretion of oxalate during immediate post-transplantation period.

Adult↗
PubMed1987

Post-surgical deterioration of renal function in primary hyperoxaluria.

Primary hyperoxaluria leading to calcium oxalate urinary stones and renal deposits occurs rarely in adults. We report three cases in whom end-stage renal failure was precipitated by urological surgery. In contrast, in one case renal stones were destroyed by extracorporeal shock-wave lithotripsy and renal function was not significantly altered. This emphasises the need for early diagnosis. This may not be easy in adult patients: urolithiasis may not be severe, radiological nephrocalcinosis may be lacking, and renal failure may develop late in life.

Adult↗
PubMed1995

[Primary hyperoxaluria].

Primary hyperoxalurias are inborn errors of metabolism with recessive autosomal transmission. Type 1 is due to the deficiency of the hepatic-specific peroxisomal enzyme alanine: glyoxylate aminotransferase, and type 2 to that of the glyoxylate reductase/D-glycerate dehydrogenase, present in the cytosol of hepatocytes and leucocytes. Type 3 is due to increased intestinal absorption of oxalate of unknown pathophysiology. In the 3 types, increased oxalate load may lead to systemic oxalosis when glomerular filtration rate decreases below 30 ml/min/1.73 m2, calcium oxalate saturation occurring in plasma when oxalate level approximates 50 mumol/l. High fluid intake and long-term co-administration of pyridoxine and orthophosphate could perhaps efficiently prevent renal failure in a majority of patients. However, combined liver-kidney transplantation presently constitutes the most adequate therapy of end-stage renal failure in type 1 and perhaps in type 2 hyperoxaluria.

Child↗
PubMed1986

Radiological aspects of primary hyperoxaluria.

Primary hyperoxaluria is a rare metabolic disorder characterized by excessive synthesis and urinary excretion of oxalate. Nephrocalcinosis with or without calcium oxalate nephrolithiasis leads to renal failure in infancy through young adulthood. Oxalosis is the condition in which the highly insoluble calcium oxalate crystals are deposited in extrarenal tissues including bone, blood vessels, heart, and the male urogenital system. The radiographic abnormalities in 14 patients with primary hyperoxaluria are described. These abnormalities include nephrolithiasis, nephrocalcinosis, dense vascular calcifications, abnormal bone density, and characteristic metaphyseal abnormalities. Changes of renal osteodystrophy and pathologic fractures are common. Radiographic bone abnormalities are dependent on the age of the patient when renal failure occurred and the degree of success of renal transplantation. Characteristic skeletal changes are present in six of seven patients who developed renal failure when less than 7 years of age.

Adolescent↗
PubMed2003

A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria.

Primary hyperoxaluria (PH) is a heterogeneous disease with a variable age of onset and a variable progression into kidney failure. Early diagnosis is mandatory to avoid the damaging effects of systemic calcium oxalate deposition. In 1997, we initiated a nationwide survey of American nephrologists to ascertain epidemiological data and current practices. PH was reported in only 102 patients, with PH I in 79 and PH II in 9; 14 patients were not classified. Most patients were Caucasian (84%). Main symptoms at diagnosis were urolithiasis (54.4%) and nephrocalcinosis (30%). A significant delay of diagnosis was seen in 42% of patients and 30% of patients were diagnosed only at end-stage renal disease (ESRD). Diagnosis was usually based on history and urinary oxalate excretion. Glycolate and l-glyceric acid excretion were rarely determined. To determine the enzyme defect, a liver biopsy was performed in 40%. Even at ESRD, only 56% of patients received an adequate diagnostic work-up. Half of the patients showed 'good' or 'fair' pyridoxine sensitivity. In addition to B(6), most patients received either citrate or orthophosphate. Kidney transplantation (KTx) failed in 19 of 32 transplants ( n=27 patients) and was due to recurrent oxalosis in 8 transplants. Liver Tx was performed after KTx in 5 patients (1 patient died). Combined liver-kidney Tx in 21 patients (in 9 patients after failure of KTx) achieved good organ function in 13 patients; 7 patients, however, died shortly after transplantation. In conclusion, the time between first symptom and diagnosis of PH must be minimized, and the diagnostic procedures have to be improved. The cases of unclassified hyperoxaluria suggest the possibility of additional type(s) of PH. As isolated KTx failed in 59% of patients, combined liver-kidney Tx seems to be the better choice in place of isolated KTx as the primary transplant procedure.

Adolescent↗
PubMed1994

Primary hyperoxaluria.

Primary hyperoxaluria (PH) is a rare inborn error of amino acid metabolism, now genetically defined, that results in excessive production and urinary excretion of oxalate. It serves as a model of severe nephrolithiasis that requires management of urinary supersaturation to prevent the common outcome of renal failure, which can be the presenting finding: the continued oxalate excess than causes progressive systemic oxalosis (deposition). Routine kidney transplantation almost invariably fails, but a (live donor) protocol that reduces danger of the accumulated load of oxalate can reduce the risk of recurrence. The attractive (and curative) option of combined kidney/liver transplant has considerably greater risk of mortality (in the US), although the European experience is considerably better, often employed earlier in the course. Key to appropriate decisions are early recognition, certain diagnosis, testing for vitamin B6 response, and immediate planning for definitive therapy when renal function is failing. PH provides one example of the absolute need for workup of the metabolic causes of stone disease.

Europe↗
PubMed1991

Metabolism of pyridoxine in mild metabolic hyperoxaluria and primary hyperoxaluria (type 1).

Plasma pyridoxine metabolites in plasma and 4-pyridoxic acid excretions in urine were measured in normal subjects, in 7 patients with type-1 hyperoxaluria and in 8 patients with mild metabolic hyperoxaluria, while receiving various doses of pyridoxine. Compliance with ingestion of pyridoxine was verified by measuring urinary 4-pyridoxic acid. In the normal subjects the maximum level of pyridoxal phosphate was obtained after only 10 mg/day of pyridoxine. The patients were divided into nonresponders, good responders and poor responders to pyridoxine according to the fall in urinary oxalate and glycollate excretions. In patients taking pyridoxine, the plasma pyridoxal phosphate levels were as for normal subjects in primary hyperoxaluria, lower than for normal subjects in mild metabolic hyperoxaluria (p less than 0.01), and in the latter group lower in partial responders than in good responders (p = 0.04). Hence in mild metabolic hyperoxaluria there may be difficulty in converting pyridoxine to pyridoxal phosphate.

Chromatography, High Pressure Liquid↗
PubMed2002

Genetic analysis--a diagnostic tool for primary hyperoxaluria type I.

Primary hyperoxaluria type I is an autosomal recessive metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. The diagnosis may be suspected when clinical signs and increased urinary oxalate and glycolate excretion present, and is confirmed by the measurement of decreased alanine:glyoxylate aminotransferase activity in a liver sample. The enzymatic assay is not readily available to pediatric nephrologists in many parts of the world. We describe three families from Croatia in whom the diagnosis of primary hyperoxaluria was solely based on clinical findings that included nephrolithiasis and nephrocalcinosis accompanied by increased urinary oxalates and glycolate excretion, as enzymatic assays of liver samples could not be performed. Mutation analysis of the AGXT gene encoding the defective enzyme confirmed the diagnosis, revealing three alleles carrying the C156ins mutation and two the G630A mutation. Screening first-degree relatives for the relevant mutation disclosed an asymptomatic affected sibling. Mutation analysis of the AGXT gene is a non-invasive and accurate tool for the diagnosis of type I primary hyperoxaluria that may replace enzymatic assays of liver biopsies.

Adult↗
PubMed1990

Primary hyperoxaluria type I.

Primary hyperoxaluria type I is a metabolic disorder caused by the deficiency of the peroxisomal alanine:glyoxylate aminotransferase. The disease is inherited as an autosomal recessive trait. The clinical course is outlined based on data from 330 published cases. Diagnostic cornerstones are clinical parameters, urinary excretion of oxalate and glycolate, and the determination of enzyme activity in liver tissue. Principles of conservative treatment, e.g. volume load and pyridoxine substitution, are described as well as experience with different modes of dialysis and transplantation. Kidney transplantation is associated with a high rate of recurrence of the original disease despite excellent management resulting in many instances in early graft loss. Liver transplantation offers the possibility to correct the metabolic defect and to prevent the progression of crystal deposition in the body.

Age Factors↗