Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene.

[primary hyperoxaluria type 1]

Primary hyperoxaluria type 1 (PH 1 ) is an autosomal recessive , inherited disorder of glyoxylate metabolism arising from a deficiency of the alanine :glyoxylate aminotransferase (AGT ) enzyme , encoded by the AGXT gene . The disease is manifested by excessive endogenous oxalate production , which leads to impaired renal function and associated morbidity . At least 146 mutations have now been described , 50 of which are newly reported here . The mutations , which occur along the length of the AGXT gene , are predominantly single -nucleotide substitutions (75 %), 73 are missense , 19 nonsense , and 18 splice mutations ; but 36 major and minor deletions and insertions are also included . There is little association of mutation with ethnicity , the most obvious exception being the p .Ile 244 Thr mutation , which appears to have North African /Spanish origins . A common , polymorphic variant encoding leucine at codon 11 , the so -called minor allele , has significantly lower catalytic activity in vitro , and has a higher frequency in PH 1 compared to the rest of the population . This polymorphism influences enzyme targeting in the presence of the most common Gly 170 Arg mutation and potentiates the effect of several other pathological sequence variants . This review discusses the spectrum of AGXT mutations and polymorphisms , their clinical significance , and their diagnostic relevance .

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Diseases presenting "which leads to impaired renal function and associated morbidity" symptom

primary hyperoxaluria type 1

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