Dialysis

Abstract Most cases of primary hyperoxaluria are due to deficiency of hepatic peroxisomal alanine:glyoxylate aminotransferase [i.e. primary hyperoxaluria type 1 (PHI), McKusick 259900] and several hundred examples have been described since the original report in 1925. By contrast, primary hyperoxaluria type 2 (PH2, McKusick 260000) is very rare indeed with only 22 patients recorded since the original description in 1968. PH2 is characterized by hyperoxaluria and L-glyceric aciduria and is caused by deficiency of r> glycerate dehydrogenase/glyoxylate reductase. In com-parison with PHI much less is known about PH2 and considerable uncertainties remain about its frequency, clinical course and optimum management. Key words: primary hyperoxaluria type 2; L-glyceric aciduria; r>glycerate dehydrogenase; oxalate Biochemistry In primary hyperoxaluria type 2 (PH2) the meta-bolic abnormality [1] affects the glycerate path-way (r>glycerate<-+hydroxypyruvate<->serine) which is analogous to the glycolate pathway (glycolate*-* glyoxylate^glycine) which is abnormal in PHI. The glycolate and glycerate pathways form part of the oxidative photosynthetic cycle in plants but have not been demonstrated in mammals, The deficient enzyme in PH2, D-glycerate de-hydrogenase (DGDH), is identical to glyoxylate reductase (GR) [2] and so catalyses the reduction of hydroxypyruvate to D-glycerate and the reduction of glyoxylate to glycolate, using NAD(H) and NADP(H) as co-factors (Figure 1). The hyperoxaluria is thought to result from an accumulation of glyoxylate in the cytosol, leading to increased oxalate synthesis mediated by LDH. Elevated concentrations of hydro-xypyruvate would result from impaired metabolism via DGDH and its further reduction via LDH would account for the L-glyceric aciduria. Absent DGDH/GR activity has been demonstrated in both leucocytes [1,4