Peroxisomal alanine:glyoxylate aminotransferase deficiency in primary hyperoxaluria type I

Danpure, Christopher J.; Jennings, Patricia R.

doi:10.1016/0014-5793(86)80563-4

Cited by 323 publications

(124 citation statements)

References 26 publications

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“…Although AGT activity was present at the top of the gradient, little or no 40 kDa protein was found there. This activity is probably due to a different enzyme, GGT [2]. In the CRM + homozygote PH 1 liver, the distribution of the immunoreactive 40 kDa protein was similar to that in the heterozygote, i.e.…”

Section: Resultsmentioning

confidence: 69%

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Immunological heterogeneity of hepatic alanine:glyoxylate aminotransferase in primary hyperoxaluria type 1

Wise¹,

Danpure²,

Jennings³

1987

FEBS Letters

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Immunoblotting of human liver sonicates, after SDS-polyacrylamide gel electrophoresis, demonstrated the presence of a 40 kDa protein, corresponding to the subunit of alanineglyoxylate aminotransferase, in six controls and three patients with primary hyperoxaluria type 1 (peroxisomal alanineglyoxylate aminotransferase deficiency). This immunoreactive 40 kDa protein was absent in a further nine patients. Subcellular fractionation of patients' livers showed that the 40 kDa protein, when present, was located mainly in the peroxisomes. In a heteroxygote liver, the 40 kDa protein was also mainly peroxisomal and paralleled the distribution of alanine:glyoxylate aminotransferase activity.

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Section: Resultsmentioning

confidence: 69%

“…The cause of the disease has been shown to be a deficiency of the hepatic peroxisomal enzyme alanine : glyoxylate aminotransferase (EC 2.6.1.44) [2]. There is considerable clinical heterogeneity within PH 1, which is to some extent paralleled by enzymic heterogeneity [3].…”

Section: Introductionmentioning

confidence: 99%

Immunological heterogeneity of hepatic alanine:glyoxylate aminotransferase in primary hyperoxaluria type 1

Wise¹,

Danpure²,

Jennings³

1987

FEBS Letters

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“…In PH-I, deficiency and/or subcellular mistargeting from peroxisomes to mitochondria of the hepatic enzyme alanine:glyoxylate aminotransferase (AGT) result in markedly increased production of oxalate by the liver. 2 Because oxalate is eliminated primarily by renal excretion and there are no known metabolic pathways for its degradation, marked hyperoxaluria ensues. Calcium oxalate deposition causing urolithiasis or nephrocalcinosis occurs early in the course of the disease.…”

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confidence: 99%

Combined liver-kidney and kidney-alone transplantation in primary hyperoxaluria

Monico

Milliner

2001

Liver Transplantation

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Combined liver-kidney and kidney-only transplantation outcomes in primary hyperoxaluria (PH) are described. Strategies for the selection of type and timing of transplantation and pretransplantation and posttransplantation management are reviewed. Records were reviewed for 16 patients with PH who received 9 liver-kidney and 10 kidney-only transplants. Plasma oxalate values declined from 61 ؎ 42 mol/L pretransplantation to 9 ؎ 6 mol/L 1 month after transplantation in liver-kidney transplant recipients and 92 ؎ 19 to 9 ؎ 5 mol/L in kidney-only transplant recipients. In most liver-kidney transplant recipients, hyperoxaluria persisted for 6 to 18 months after transplantation. Follow-up was 3.5 ؎ 4.1 years in liver-kidney and 4.5 ؎ 6.3 years in kidney-alone transplant recipients. Patient survival rates were 78% for liver-kidney and 89% for kidney-only transplant recipients. No hepatic allografts were lost. Three of 9 liverkidney and 6 of 10 kidney-alone transplants lost renal allograft function. In those with functioning kidneys, renal clearance was 45.1 ؎ 19.5 mL/min/1.73 m 2 in liverkidney transplant recipients and 49.5 ؎ 26.1 mL/min/ 1.73 m 2 in kidney-only transplant recipients at last follow-up. Kaplan-Meier 1-, 2-, 3-, and 5-year renal allograft survival rates for patients undergoing transplantation after 1984 were 78%, 78%, 52%, and 52% in liver-kidney transplant recipients and 86%, 71%, 54%, and 36% in kidney-only transplant recipients. Simultaneous grafting of liver and kidney after the development of renal insufficiency is recommended for the majority of patients with PH type I (PH-I). Kidney-alone transplantation is recommended for those with pyridoxine-responsive type I disease because pharmacological therapy allows favorable management of oxalate production in this situation. Kidney-alone transplantation also is recommended for PH type II (PH-II). This disease is less severe than PH-I, and it is currently unknown whether liver transplantation will correct the metabolic defect responsible for PH-II. (Liver Transpl 2001;7:954-963.)

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“…4 In 1986, Danpure and Jennings found a low or absent activity of liver-specific peroxisomal alanine-glyoxylate aminotransferase, which normally catalyzes the transamination of glyoxylate to glycine, to be causal in patients with PH I. 8 Less AGT activity may also be provoked by peroxisomal to mitochondrial mistargeting, with inefficient AGT in the mitochondrion. Primary hyperoxaluria has to be differentiated from secondary forms, e.g., in chronic inflammatory bowel disease, or after ileum resection, when malabsorption of fatty and bile acids leads to an increase in oxalate absorption.…”

Section: Discussionmentioning

confidence: 99%

Primary Hyperoxaluria Type I and Urolithiasis in Children: Report of Three Cases

et al. 1997

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Primary hyperoxaluria type I (PH I) is an autosomal recessive inherited disease 1,2 with an annual incidence of approximately one to two patients per million. 3 It is caused by a low or absent activity of the liver-specific peroxisomal alanine-glyoxylate aminotransferase, 4 leading to an increase in urinary excretion of oxalate and glycolate. Thereby, urinary saturation for calcium-oxalate is elevated, leading to crystal formation, urolithiasis and/or medullary nephrocalcinosis. Disease progression causes systemic oxalosis with deposition of oxalate in parenchymatous organs, bones and retina.1 In most patients this disorder is not recognized until mid-childhood or early adulthood, due to symptoms mainly related to recurrent renal stones or chronic renal failure.5 Therefore, although the first symptoms are usually present in early childhood, the diagnosis of this devastating disease is frequently not made until systemic signs and end-stage renal disease are present. The prognosis for the untreated disease is poor, leading to death around the age of 20 due to renal failure, or even earlier in the infantile forms of PH I. Early detection and metaphylaxis is crucial in order to improve disease prognosis. 5 The appropiate urologie evaluation, management and treatment is still controversial.We report here the case of three children from a Libyan family diagnosed to have PH I. The family consisted of unrelated healthy parents with three healthy sisters and two healthy brothers. There were two neonatal deaths of unknown causes. There were no other known cases of PH in the extended family.The investigations and the clinical course are described, as well as our experience with different models of stone removals. Finally, the role of extra-corporeal shock wave lithotripsy (ESWL) in the treatment of stones in PH I is discussed. Case Reports Case 1Together with his two older siblings, a seven-year-old Libyan boy was referred to the University Children's Hospital for a diagnostic workup. He had a previous history of recurrent urolithiasis and end-stage renal failure.Maintenance hemodialysis was started in April 1994 in Libya after a right-sided ureterolithotomy to remove an obstructive stone. Renal failure had already been diagnosed before the operation, and hypertension, anemia and growth failure were present. Oxalate depositions on the retina were seen by fundus examination.Upon admission, abdominal x-ray showed multiple renal stones of various sizes ( Figure 1) and medullary nephrocalcinosis was seen in ultrasound. Serum creatinine was 733 μmol/L, blood urea was 31.6 mmol/L, plasma oxalate was 72 μmol/L (normal 2-6 μmol/L 6 ). Urinary oxalate excretion was "low" due to end-stage renal failure (0.3 mmol/1.73 m 2 /24h), oxalate/creatinine ratio was 199 mmol/mol (age-related normal value: 38-132 mmol/L 7 ), the ratio of glycolate over creatinine in urine was 88 mmol/mol (normal 18-92 mmol/mol 7 ). A liver biopsy specimen showed a decreased antiglobulin test (AGT) of only 1.5 μmol/h/mg protein (normal 3.2-9.0 8 ) and only a we...

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Peroxisomal alanine:glyoxylate aminotransferase deficiency in primary hyperoxaluria type I

Cited by 323 publications

References 26 publications

Immunological heterogeneity of hepatic alanine:glyoxylate aminotransferase in primary hyperoxaluria type 1

Immunological heterogeneity of hepatic alanine:glyoxylate aminotransferase in primary hyperoxaluria type 1

Combined liver-kidney and kidney-alone transplantation in primary hyperoxaluria

Primary Hyperoxaluria Type I and Urolithiasis in Children: Report of Three Cases

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