Biochemical and genetic diagnosis of the primary hyperoxalurias: A review

Background and Purpose: The primary hyperoxalurias are a group of inherited disorders of endogenous oxalate overproduction, Diagnosis of the two best- characterized disorders, primary hyperoxaluria (PH) Types 1 and 2, is achie ved by sequential measurement of alanine:glyoxylate aminotransferase and gl yoxylate reductase enzyme activity in a single needle liver biopsy, While g enetic analysis of PH2 is still at a relatively early stage, the AGXT gene defective in the Type 1 disorder is well characterized, and a number of mut ations have been identified, Methods: To determine whether mutation analysis could replace enzymatic ana lysis for the diagnosis of PH1, DNA samples from 127 consecutive unrelated patients in whom there was a high clinical suspicion of primary hyperoxalur ia were analyzed for the presence of the G630A and T853C mutations, which t ogether account for approximately 34% of the mutant alleles in our patient cohort. Results and Conclusions: The sensitivity of mutation detection was 47% in t hose patients with enzymologically confirmed Type 1 disease, showing that m utation analysis cannot effectively replace enzymology at the present time. However, there is little doubt of the value of genetic methods (mutation a nd linkage analysis) for diagnosing PH1 land eventually PH2) in other famil y members and for prenatal diagnosis and carrier testing.