Disease relevance of Hyperoxaluria, Primary

• Successful treatment of infantile type I primary hyperoxaluria complicated by pyridoxine toxicity [1].
• Alanine/glyoxylate aminotransferase 1 (AGT) is peroxisomal in most normal humans, but in some patients with the hereditary disease primary hyperoxaluria type 1 (PH1), AGT is mislocalized to the mitochondria [2].
• A 23-year-old man with type 1 primary hyperoxaluria, renal failure, and oxalosis developed a severe cardiomyopathy while awaiting combined liver-kidney transplantation [3].
• The pathways of oxalate synthesis in humans are not well defined despite their clinical significance in primary hyperoxaluria and idiopathic calcium oxalate nephrolithiasis [4].
• BACKGROUND: Calcium-oxalate (CaOx) deposition and systemic oxalosis are uncommon in children with chronic renal failure (CRI), but frequent in children with primary hyperoxaluria type I (PH-1) [5].

High impact information on Hyperoxaluria, Primary

• Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria [6].
• All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit [7].
• In two patients with type I primary hyperoxaluria, urinary oxalate and glycolate excretion fell markedly in response to a physiologic dose of pyridoxine of 2 mg per day and became completely normal when the dose was increased to 25 mg per day [8].
• We measured urinary oxalate and glycolate excretion before and during pyridoxine administration (2 to 200 mg per day) in four patients with primary hyperoxaluria [8].
• Enzymological diagnosis of primary hyperoxaluria type 1 by measurement of hepatic alanine: glyoxylate aminotransferase activity [9].

Chemical compound and disease context of Hyperoxaluria, Primary

• Response to a physiologic dose of pyridoxine in type I primary hyperoxaluria [8].
• Treatment of patients with primary hyperoxaluria with orthophosphate and pyridoxine decreases urinary calcium oxalate crystallization and appears to preserve renal function [6].
• Identification of mutations associated with peroxisome-to-mitochondrion mistargeting of alanine/glyoxylate aminotransferase in primary hyperoxaluria type 1 [10].
• ATP-dependent degradation of a mutant serine: pyruvate/alanine:glyoxylate aminotransferase in a primary hyperoxaluria type 1 case [11].
• We have previously shown that in some patients with primary hyperoxaluria type 1 (PH1), disease is associated with mistargeting of the normally peroxisomal enzyme alanine/glyoxylate aminotransferase (AGT) to mitochondria (Danpure, C.J., P.J. Cooper, P.J. Wise, and P.R. Jennings. J. Cell Biol. 108:1345-1352) [10].

Biological context of Hyperoxaluria, Primary

• An intronic duplication in the alanine: glyoxylate aminotransferase gene facilitates identification of mutations in compound heterozygote patients with primary hyperoxaluria type 1 [12].
• We report here the identification of a duplication within the first intron of the gene encoding human alanine:glyoxylate aminotransferase (AGT); this duplication is closely linked to two point mutations associated with peroxisome-to-mitochondrion mistargeting of AGT in primary hyperoxaluria type 1 (PH1) patients [12].
• We describe a novel missense mutation (A112D) and polymorphism (V326I) in the human AGT gene in two black African patients with primary hyperoxaluria type 1, an autosomal recessive disease resulting from a deficiency of the liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44) [13].
• In order to identify additional genotypes in primary hyperoxaluria type 1, we sequenced the AGXT genes of 9 patients [14].
• Maternal isodisomy of the telomeric end of chromosome 2 is responsible for a case of primary hyperoxaluria type 1 [15].

Anatomical context of Hyperoxaluria, Primary

• An enzyme trafficking defect in two patients with primary hyperoxaluria type 1: peroxisomal alanine/glyoxylate aminotransferase rerouted to mitochondria [16].
• Oxalate synthesis in human hepatocytes is not well defined despite the clinical significance of its overproduction in diseases such as the primary hyperoxalurias [17].
• In one third of patients with the autosomal recessive disease primary hyperoxaluria type 1, there is a further redistribution of AGT so that the great majority (approximately 90%) is located in the mitochondria and only a small minority (10%) in the peroxisomes [18].
• It is probable that chronic hemodialysis favors the deposition of oxalate in the Schwann cells and the development of neuropathy in patients with primary hyperoxaluria and renal failure [19].
• Prenatal diagnosis has been performed by measuring AGT enzyme activity and immunoreactive AGT protein on liver biopsies from two fetuses at risk for primary hyperoxaluria type 1 [20].

Gene context of Hyperoxaluria, Primary

• Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44) [21].
• The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II [22].
• 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) [23].
• BACKGROUND: A definitive diagnosis of primary hyperoxaluria type 1 (PH1) and primary hyperoxaluria type 2 (PH2) requires the measurement of alanine:glyoxylate aminotransferase (AGT) and glyoxylate reductase (GR) activities, respectively, in a liver biopsy [24].
• Primary hyperoxaluria type II (PH-II) or L-glyceric aciduria was first reported by Williams and Smith in 1968 (N Engl J Med 278:233-239, 1968) [25].

Analytical, diagnostic and therapeutic context of Hyperoxaluria, Primary

• Oxalate balance studies in patients on hemodialysis for type I primary hyperoxaluria [26].
• Oxalate dynamics and removal rates during haemodialysis and peritoneal dialysis in patients with primary hyperoxaluria and severe renal failure [27].
• Potential for bilateral nephrectomy to reduce oxalate release after combined liver and kidney transplantation for primary hyperoxaluria type 1 [28].
• Fetal liver alanine: glyoxylate aminotransferase and the prenatal diagnosis of primary hyperoxaluria type 1 [20].
• Oral administration of SPP to control subjects, recurrent stone formers and patients with primary hyperoxaluria resulted in an overall increase of 8% (P less than 0.01) in the polyanionic inhibition of CaOx crystallisation in urine as measured by the zeta potential [29].

References