Aims To assess the relevance of the newly discovered gene DHDPSL underlying primary hyperoxaluria type 3 (PH3) in a UK paediatric stone centre.
Background Children with renal calculi undergo a metabolic evaluation and those with persistent hyperoxaluria (approximately 15% of stone formers) have either a secondary cause for this or are screened for genetic defects in oxalate metabolism (PH) Until recently, two types were known: PH1 is due to defective production, localisation or function of AGT and PH2 to defective production of GRHPR. Recently, a third type of PH3 was described in which patients have mutations in DHDPSL, the gene encoding 4-hydroxy-2-oxoglutarate aldolase, catalyzing the final step in the metabolic pathway of hydroxyproline.1
Methods We screened all children with atypical PH for mutations in DHDPSL. Atypical PH was defined as persistent hyperoxaluria and no identifiable mutation in AGT and GRHPR and/or normal enzyme activity in a liver biopsy.
Results Four children with atypical PH were identified. All were found to carry bi-allelic DHDPSL mutations. Clinical, biochemical and genotype results are shown in the table 1.
Conclusions These results demonstrate PH3 as a cause of renal calculi in children. Besides identifying the cause, the demonstration of a genetic basis has implications for recurrent stone formation and for family counselling. The age of presentation varies from 5 months to 12 years, in keeping with the heterogeneity seen in other disorders of nephrolithiasis. However, in this small series, the degree of hyperoxaluria was moderate reinforcing the need for a thorough metabolic and if necessary genetic evaluation of all children with renal stones.
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