Genetic basis of primary hyperoxaluria type II.
Primary hyperoxaluria Type II (PH2) is a rare monogenic disease characterized by excessive urinary oxalate and L-glycerate excretion. The severity of clinical complications in PH2 patients can range from none to end-stage renal failure secondary to massive deposits of calcium oxalate crystals in the kidney. The disease is a result of the absence of an enzyme with glyoxylate reductase and hydroxypyruvate reductase activities (GRHPR). Recent breakthroughs have occurred in our understanding of the molecular basis of PH2. In this article, we briefly review the literature concerning the clinical and biochemical characteristics of the disease and the enzyme associated with it. We describe the identification of the cDNA for the GRHPR enzyme using the expressed sequence tag database, the characterization of the human GRHPR gene, and the identification of mutations in patients with PH2. Insights gained from the molecular biology underlying this disease as they relate to relevant clinical issues such as potential therapeutic strategies are discussed.
Webster
K E
KE
Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Cramer
S D
SD
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002899:Chromosomes, Human, Pair 9; D018076:DNA, Complementary / Q000378:metabolism; D020224:Expressed Sequence Tags; D005988:Glyceric Acids / Q000652:urine; D006801:Humans; D050537:Hydroxypyruvate Reductase; D006960:Hyperoxaluria, Primary / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010070:Oxalates / Q000652:urine; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D005988:Glyceric Acids; D010070:Oxalates; D000429:Alcohol Oxidoreductases; C020830:glyoxylate reductase; D050537:Hydroxypyruvate Reductase