Strategies for the prenatal diagnosis of primary hyperoxaluria type 1

Abstract

Primary hyperoxaluria type 1 (PH1) is a potentially lethal autosomal recessive disorder of glyoxylate metabolism caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Over the past 13 years, various strategies have been adopted for its prenatal diagnosis, including (1) glyoxylate metabolite analysis of amniotic fluid in the second trimester; (2) AGT enzyme assay, immunoassay, and immuno-electron microscopy of fetal liver biopsies also in the second trimester; and (3) linkage and mutation analysis of DNA isolated from chorionic villus samples in the first trimester. These methods have evolved in parallel with our increased understanding of the molecular aetiology and pathogenesis of the disease. Although the usefulness of metabolite analysis remains unproven, all the other methods have been successfully applied to the prenatal diagnosis of PH1. In this review, examples of the use of the available methodologies are provided, and their pros and cons are discussed with reference to specific cases.