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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxaluria type I (HPI) is a metabolic disorder secondary to liver alanine glyoxylate aminotransferase deficiency. Renal failure occurs due to the excessive production and precipitation of oxalate in the kidney. Combined liver-renal transplantation is the correct treatment for this condition when end-stage renal failure occurs as with renal transplantation alone the risk of recurrence of the same pathology in the transplanted kidney would be high. We report the case of a 4 year-old child with HPI suffering from terminal renal failure in whom a hepato-renal transplantation was performed: six months later, creatinine clearance was 62 ml/min/1.73 m2 and liver function tests were normal.
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PMID:[Hepatic and renal transplantation in the treatment of type I hyperoxaluria]. 176 34

We have studied the characteristics of human liver alanine-glyoxylate aminotransferase, which is deficient in hyperoxaluria type I, an inherited disorder of glyoxylate metabolism. The enzyme was optimally active at pH 8.0 showing apparent Km values for L-alanine and glyoxylate of 8.3 and 1.3 mmol/l, respectively. Activity was found to proceed linearly for up to 4 h. Measurements under these optimal conditions enabled the biochemical diagnosis of hyperoxaluria type I to be made via enzyme activity measurements in percutaneous needle biopsy specimens of liver tissue.
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PMID:Human liver L-alanine-glyoxylate aminotransferase: characteristics and activity in controls and hyperoxaluria type I patients using a simple spectrophotometric method. 239 96

Peroxisomes play an essential role in human cellular metabolism. Peroxisomal disorders, a group of genetic diseases caused by peroxisomal dysfunction, can be classified in three groups namely a group of disorders with a general peroxisomal dysfunction (Zellweger syndrome; infantile type of Refsum's disease; neonatal adrenoleukodystrophy, hyperpipecolic acidemia), a group with an impairment of some, but not all peroxisomal functions (rhizomelic chondrodysplasia punctata) and a group with impairment of only a single peroxisomal function (acatalasemia, X-linked adrenoleukodystrophy/adrenomyeloneuropathy; adult type of Refsum's disease; peroxisomal thiolase deficiency; peroxisomal acyl-CoA oxidase deficiency; hyperoxaluria type I). In this paper we report the typical findings in ophthalmological examinations of patients suspected of Zellweger syndrome contributing to the clinical diagnosis of this disorder. In biochemical studies using a rapid gaschromatographic detection method for plasmalogens we confirmed that plasmalogens are severely deficient in all tissues of Zellweger patients studied. Moreover, using a recently developed radiochemical method, de novo plasmalogen biosynthesis was found to be impaired in fibroblasts from patients with Zellweger syndrome, infantile Refsum's disease, neonatal adrenoleukodystrophy or rhizomelic chondrodysplasia punctata, this in contrast to X-linked chondrodysplasia in which a normal plasmalogen biosynthesis was found. From the literature it is known that peroxisomal beta-oxidation with both long-chain (C16:0) and very long-chain (C24:0; C26:0) fatty acids is deficient in Zellweger syndrome, infantile Refsum's disease and neonatal adrenoleukodystrophy. In contrast, in X-linked adrenoleukodystrophy only the peroxisomal beta-oxidation of the very long chain fatty acids is impaired. As a result very long-chain fatty acids accumulate in tissues, plasma, fibroblasts and amniotic fluid cells from patients with Zellweger syndrome, infantile Refsum's disease, neonatal and X-linked adrenoleukodystrophy, but not in rhizomelic chondrodysplasia punctata or X-linked chondrodysplasia. Finally we confirmed that the peroxisomal enzyme alanine glyoxylate aminotransferase is severely deficient in liver from a patient that died because of the neonatal type of hyperoxaluria type I, but not in liver from Zellweger patients.
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PMID:Genetic diseases caused by peroxisomal dysfunction. New findings in clinical and biochemical studies. 344 Apr 44

We have studied the urinary excretion of oxalate and glycollate in patients with the Zellweger syndrome and hyperoxaluria type I and have measured the activity of alanine glyoxylate aminotransferase (a peroxisomal enzyme in man) in the patients. In agreement with earlier reports we found that alanine glyoxylate aminotransferase was strongly deficient in liver from a hyperoxaluria type I patient, thus explaining the increased urinary excretion of oxalate and glycollate in these patients. In livers from Zellweger patients, however, in which morphologically distinguishable peroxisomes are absent, the enzyme was not deficient, which is in accordance with our finding that the urinary excretion of oxalate and glycollate was normal in these patients.
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PMID:Alanine glyoxylate aminotransferase and the urinary excretion of oxalate and glycollate in hyperoxaluria type I and the Zellweger syndrome. 365 53

In this paper we studied the glyoxylate-dependent transamination of L-alanine and L-glutamate in human liver homogenates in order to develop a reliable method for the determination of true alanine:glyoxylate aminotransferase activity in liver homogenates from patients suspected to suffer from hyperoxaluria type I. Measurements were made according to two protocols described in literature in control human liver homogenates which were either untreated or treated with an antiserum raised against purified alanine:glyoxylate aminotransferase. The results obtained show that enzyme activity can best be determined at pH 8.0 as compared to pH 7.4 since the former leads to a higher sensitivity of the method. Alanine:glyoxylate aminotransferase activities measured at pH 8.0 are approximately 50% higher compared to the enzyme activities measured at pH 7.4. Accordingly, it is proposed to measure alanine:glyoxylate aminotransferase activity at pH 8.0 using the newly determined correction factor as described in this paper.
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PMID:Re-evaluation of conditions required for measurement of true alanine:glyoxylate aminotransferase activity in human liver: implications for the diagnosis of hyperoxaluria type I. 797 3

Two patients with atypical manifestations of aberrant peroxisomal biogenesis are described. Contrary to previous studies, which had shown that Zellweger syndrome patients usually have normal levels of urinary oxalate excretion, the patients in the present study had evidence of abnormal oxalate metabolism in the form of hyperoxaluria and, in one of the patients, calcium oxalate urolithiasis. Activity of the liver-specific peroxisomal enzyme alanine:-glyoxylate aminotransferase (AGT), which is a major determinant of the level of endogenous oxalate synthesis in humans, was normal in one patient and markedly supranormal in the other. Using the technique of post-embedding protein A-colloidal gold immunoelectron microscopy, AGT was found to be mainly cytosolic in the livers of both patients, with significant amounts also localized in the nuclei. In a small minority of the hepatocytes of one patient, who was homozygous for the more common (major) AGT allele, large numbers of unidentified fibrillar arrays were found in the cytosol, which labelled heavily for immunoreactive AGT. The background cytosolic AGT labelling was markedly reduced in such cells when compared to the majority of cells that did not contain fibrils. In the other patient, who was heterozygous for the major and minor AGT alleles, there appeared to be low levels of mitochondrial AGT labelling. In the light of these data, the possible metabolic function of cytosolic AGT in the livers of panperoxisomal disease patients is discussed.
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PMID:Cytosolic compartmentalization of hepatic alanine:glyoxylate aminotransferase in patients with aberrant peroxisomal biogenesis and its effect on oxalate metabolism. 805 36

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.
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PMID:[Primary hyperoxaluria]. 852 46

Type I primary hyperoxaluria is an uncommon disease related to alanine glyoxylate aminotransferase (AGT) deficiency, an exclusively hepatic enzyme. AGT deficiency leads to an overproduction of oxalate in the liver and consequent hyperoxalemia and massive hyperoxaluria with renal failure. The diagnosis is confirmed by needle biopsy of the kidney showing the exact nature of the enzyme deficiency. When terminal renal failure has developed there are two therapeutic possibilities: kidney graft or a double liver-kidney graft. Kidney graft alone is often insufficient and carries the risk of recurrent disease in the graft since the liver disorder has not been corrected. Inversely, combined liver-kidney graft can not only replace the destroyed kidneys but also correct the metabolic disorder through the effect of the AGT in the donor liver. Although this approach may be successful, it is a very aggressive procedure with high mortality.
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PMID:[Mechanisms and treatment of primary type I hyperoxaluria]. 869 89

In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3-5.7 yr after performing successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m2). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m2) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.
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PMID:Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1. 1093 16

The following is a case report of a patient with type I hyperoxaluria who received a living related renal transplant for end-stage renal disease. The deficiency or complete absence of the hepatic enzyme alanine glyoxalate aminotransferase characterizes type I hyperoxaluria. When deficient, an overproduction of oxalate occurs, which then can be deposited in multiple end-organ systems. When performing surgery on a patient with type I hyperoxaluria, the anesthetist needs to be aware that these patients can have a host of problems ranging from cardiovascular anomalies to end-stage renal disease. A careful assessment of each system needs to be performed, along with vigilant planning of the anesthetic regimen. Through proper planning and implementation, a safe and effective anesthetic usually can be performed.
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PMID:Living related kidney transplantation in a 15-year-old patient with type I hyperoxaluria: a case report. 1196 60


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