diseases

Primary hyperoxaluria is a rare monogenic disorder that is caused by mutations of the GRHPR or AGXT genes in liver and other cells.¹² It affects about 1 per 60,000 to 120,000 live births. However, in order to inherit it, both parents must be carriers of the mutant gene.¹³ The disease is "characterized by a lack of the enzyme that catalyzes the reduction of hydroxypyruvate to D-glycerate, the reduction of glyoxylate to glycolate and the oxidation of D-glycerate to hydroxypyruvate"¹⁴. The substance glyoxylate is made from the breakdown of amino acids and some sugars. In normal scenarios glyoxylate gets converted into glycine or sometimes glycolate. This conversion is made possible by alanine-glyoxylate aminotransferase and glyoxylate reductase/hydroxypyruvate reductase. The mutation of the GRHPR or AGXT genes can cause a shortage of glycine and glycolate. As a result of the buildup of glyoxylate, it will subsequently be converted to oxalate, which when combined with calcium forms calcium oxilate which can damage the kidneys.¹³

PH2 was initially discovered as PH1 about thirty years ago. People with the disease experience urinating high amounts of oxalate and L-glycerate¹⁴. PH2 however, is usually not a long term kidney problem like PH1¹². PCR (Polymerase Chain Reaction) was used to study the mutation in the GRHPR gene from 365 unrelated DNA samples of patients referred for diagnosis of PH1 and/or PH2 through liver enzyme analysis. The results were that one or more mutation was found in 183 (68.8%) of proven cases of PH1 and PH2. The patients were homozygous, thus a molecular diagnosis was possible¹⁵. Research has found five mutations that are believed to cause PH (article exerpt)¹⁶. This study found that a gene mutated with any of the five mutations will results in a lack of enzyme production and thus buildup of glyoxylate.

There are about 1,000 people afflicted with PH, dialysis and kidney transplants only offer temporary relief. The only procedure which seems to have some success is a joint kidney-liver transplant. Many PH patients will be die of renal failure before their first birthday. While there is no known cure for the disease, a careful diet including Vitamin B6 in addition to urine crystalline inhibitors can alleviate the negative effects of the disease. "For those who survive infancy, the usual course of events is a gradual decline in renal function over a period of years and a characteristically short final stage with the onset of chronic renal failure, which may appear in early childhood but which regularly occurs in late childhood or early adult life." In 1999 a publication from Saudi Arabia showed that all 16 patients studied reached end stage renal disease within six months to two years. "In general, one-half of all patients reach end stage renal disease before 25 years of age."¹⁷