THE PRIMARY HYPEROXALURIAS: AN UPDATE ON DIAGNOSIS AND TREATMENT

von Schnakenburg. C., Latta, K., Rumsby, G.

Kinderklinik der Medizinischen Hochschule Hannover, Germany and Dept. of Chemical Pathology, University College London Hospitals

INTRODUCTION: Primary hyperoxaluria (PH) is a rare condition causing nephrocalcinosis, urolithiasis and end stage renal failure in childhood. Type 1 has been extensively studied during the last decade, since a common genetic variant leads to an unparalleled cellular mistargeting of the enzyme alanine: glyoxylate aminotrans-ferase from peroxisome to mitochondria. The genetic basis of type 2 primary hyperoxaluria (glyoxylate/hydroxypyruvate reductase, encoded by the gene QRHPR) has only recently been elucidated.

DIAGNOSIS: Suspicion of hyperoxaluria should be raised in all children presenting with severe nephrocalcinosis, renal stones or unexplained renal failure. Urinary oxalate should be repeatedly evaluated before hyperoxaluria can be excluded. In cases of elevated urinary oxalate, secondary causes like diet, malabsorption or intoxication have to be excluded before a diagnosis of PH is considered. Determination of urinary glycolate and glycerate may be helpful in differentiating between type 1 and 2 PH, respectively, but normal glycolate does not exclude PH1. Enzyme studies in liver biopsies are strongly recommended for a definitive diagnosis due to the severe prognostic and therapeutic implications.

TREATMENT: In addition to high fluid intake, supplementation of phosphate and citrate can be used to reduce oxalate crystallisation in the urinary tract. In some forms of type 1 PH hyperoxaluria can be reduced by oral pyridoxine. Kidney transplantation alone is associated with a high risk of recurrence. Instead, combined liver kidney transplantation is recommended to replace the deficient enzyme in type 1 PH.

OUTLOOK: Recognition of specific mutations in type 1 and recently type 2 PH have improved our diagnostic tools in these diseases. New tissue distribution studies of the enzymes involved suggest that in severe cases of type 2 as well as type 1 PH, liver transplantation should be regarded as therapeutic option.