Genetic Disorders – Development
Kidney International (2002) 62, 392–400; doi:10.1046/j.1523-1755.2002.00468.x
Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II
Carla G Monico, Mai Persson, G Charles Ford, Gill Rumsby and Dawn S Milliner
Division of Nephrology, General Clinical Research Center, Mayo Clinic Rochester, Minnesota, USA, and Department of Chemical Pathology, University College London Hospitals, London, England, United Kingdom
Correspondence: Carla G. Monico, M.D., Division of Nephrology, Mayo Clinic 200 First Street, SW, Rochester, Minnesota 55905, USA. E-mail: monico.carla@mayo.edu
Received 11 January 2002; Revised 8 March 2002; Accepted 13 March 2002.
Abstract
Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II.
Background
Hyperoxaluria may be idiopathic, secondary, or due to primary hyperoxaluria (PH). Hepatic alanine:glyoxylate aminotransferase (AGT) or glyoxylate/hydroxypyruvate reductase (GR/HPR) deficiency causes PHI or PHII, respectively. Hepatic glycolate oxidase (GO) is a candidate enzyme for a third form of inherited hyperoxaluria.
Methods
Six children were identified with marked hyperoxaluria, urolithiasis, and normal hepatic AGT (N = 5) and GR/HPR (N = 4). HPR was below normal and GR not measured in one. Of an affected sibling pair, only one underwent biopsy. GO mutation screening was performed, and dietary oxalate (Dietox), enteric oxalate absorption (EOA) measured using [13C2] oxalate, renal clearance (GFR), fractional oxalate excretion (FEox) in the children, and urine oxalate in first-degree relatives (FDR) to understand the etiology of the hyperoxaluria.
Results
Mean presenting age was 19.2 months and urine oxalate 1.3 
0.5 mmol/1.73 m2/24 h (mean SD). Two GO sequence changes (T754C, IVS3 – 49 C>G) were detected which were not linked to the hyperoxaluria. Dietox was 42 31 mg/day. EOA was 9.4 3.6%, compared with 7.6 1.2% in age-matched controls (P = 0.33). GFR was 90 19 mL/min/1.73 m2 and FEox 4.2 1.4. Aside from the two brothers, hyperoxaluria was not found in FDR.
Conclusions
These patients illustrate a novel form of hyperoxaluria and urolithiasis, without excess Dietox, enteric hyper-absorption, or hepatic AGT, GR/HPR deficiency. Alterations in pathways of oxalate synthesis, in liver or kidney, or in renal tubular oxalate handling are possible explanations. The affected sibling pair suggests an inherited basis.
Keywords:
enteric oxalate absorption, calcium oxalate urolithiasis, alanine:glyoxylate aminotransferase, stone formation, kidney stones, urolithiasis
