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Primary hyperoxalurias (PH) are very rare diseases characterised by overproduction and accumulation of oxalate in the body. The main target organ is the kidney, as oxalate cannot be metabolised and is excreted in the urine, leading to nephrocalcinosis, recurrent urolithiasis, and subsequent renal impairment. During the last decade, major advances in enzymology, molecular genetics, and cell biology have generated excellent reviews on both pathophysiology and management1 2; however, specific questions remain unanswered.
Basically, hyperoxaluria (normal urinary oxalate < 0.5 mmol/1.73 m2 per day; normal urinary oxalate to creatinine ratio < 0.10 mmol/mmol) and calcium oxalate crystallisation are the hallmarks of any kind of PH.1 The presence of monohydrated calcium oxalate crystals in the urine or tissues can be assessed by infrared spectrometry or polarised light microscopy.3Hyperoxaluria may be associated with increased urinary excretion of either glycolate in PH1 or l-glycerate in PH2, but urinary metabolites are no longer adequate for accurate diagnosis, which requires either enzyme assessment or DNA analysis.4 5
Primary hyperoxaluria type 1 (PH1)
PH1 is an autosomal recessive disorder of glyoxylate metabolism (1 in 120 000 live births in France)6 caused by deficiency of the hepatic peroxisomal pyridoxal phosphate dependent enzyme alanine-glyoxylate aminotransferase (AGT), the gene of which,AGXT (about 10 kb), has been sequenced and located on chromosome 2q37.3.2 Over 25 mutations have been identified so far, but most of them are solitary mutations, and only 25% of the patients have both alleles identified. So far, no mutation at all has been found in one third of the patients. The most common mutations (G170R and I244T) are encountered in 40% of alleles, so their identification may lead to direct diagnosis in selected populations (O Basmaison 1999, personal communication).7 8 The disease occurs either because AGT activity is undetectable (two thirds) or because it …