Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II

Carla G. Monico, Mai Persson, G. Charles Ford, Gill Rumsby, Dawn S. Milliner

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-400
Number of pages9
JournalKidney international
Volume62
Issue number2
DOIs
StatePublished - Aug 2002

Keywords

  • Alanine:glyoxylate aminotransferase
  • Calcium oxalate urolithiasis
  • Enteric oxalate absorption
  • Kidney stones
  • Stone formation
  • Urolithiasis

ASJC Scopus subject areas

  • Nephrology

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