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 (Diet(ox)), enteric oxalate absorption (EOA) measured using [13C2] oxalate, renal clearance (GFR), fractional oxalate excretion (FE(ox)) 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. Diet(ox) 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 FE(ox) 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 Diet(ox), 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.
Monico
Carla G
CG
Division of Nephrology, General Clinical Research Center, Mayo Clinic Rochester, Minnesota 55905, USA. monico.carla@mayo.edu
Persson
Mai
M
Ford
G Charles
GC
Rumsby
Gill
G
Milliner
Dawn S
DS
D000429:Alcohol Oxidoreductases / Q000235:genetics; D002136:Calcium, Dietary / Q000652:urine; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006038:Glyoxylates / Q000378:metabolism; D006801:Humans; D006959:Hyperoxaluria / Q000235:genetics* / Q000378:metabolism*; D006960:Hyperoxaluria, Primary; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010070:Oxalates / Q000652:urine; D010375:Pedigree; D010710:Phosphates / Q000652:urine; D014545:Urinary Calculi / Q000235:genetics / Q000378:metabolism
D002136:Calcium, Dietary; D006038:Glyoxylates; D010070:Oxalates; D010710:Phosphates; D000429:Alcohol Oxidoreductases; C020821:glycollate oxidase; C031150:glyoxylic acid