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Primary hyperoxaluria type 1 is a rare metabolic disorder transmitted as an autosomal recessive disease. It is due to a defect of the peroxysomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). The defect in AGT, which normally converts glyoxylate to glycin, results in an increase of the glyoxylate pool, which is converted to oxalate. The first symptoms occur before one year of age in 15 percent and before 5 years of age in 50 percent. The infantile form is characterized by chronic renal failure due to massive oxalate deposition. In other patients, urolithiasis develops with infections, hematuria, renal colics or acute renal failure due to complete obstruction. End-stage renal failure occurs before 15 years of age in half the cases and the resulting increase of circulating oxalate leads to its deposition in tissues causing cardiac conduction defects, hypertension, distal gangrene, and reduced joint mobility and pain. Hyperoxaluria is associated with increased excretion of glycolate. The absence of AGT activity can be confirmed by liver biopsy. A prenatal diagnosis can be made on liver biopsy or by DNA analysis either using polymorphic markers located in the AGXT gene region on chromosome 2q36-37 when the family is informative or looking at the mutation when it has been detected in a sibling. Treatment includes high fluid intake to maintain high urine output above 3 liters/1,73m2/day, pyridoxine supplement (AGT coenzyme) and alkalinization of urine. Renal transplantation alone does not correct the metabolic disorder, which will recur in the graft. Combined liver and kidney transplantation is probably the treatment of choice in young children: transplantation should be performed before or very soon after starting dialysis in order to prevent extrarenal complications. |