TY - JOUR
T1 - Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II
AU - Monico, Carla G.
AU - Persson, Mai
AU - Ford, G. Charles
AU - Rumsby, Gill
AU - Milliner, Dawn S.
N1 - Funding Information:
This study was supported by a grant from the Oxalosis and Hyperoxaluria Foundation (OHF), and in part by GCRC grant 5M01-RR00585-23 from the National Institutes of Health. A portion of the data was published in the Proceedings of the Finlayson Symposium ( J Endurol 13:633-636, 1999).
PY - 2002/8
Y1 - 2002/8
N2 - 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.
AB - 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.
KW - Alanine:glyoxylate aminotransferase
KW - Calcium oxalate urolithiasis
KW - Enteric oxalate absorption
KW - Kidney stones
KW - Stone formation
KW - Urolithiasis
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U2 - 10.1046/j.1523-1755.2002.00468.x
DO - 10.1046/j.1523-1755.2002.00468.x
M3 - Article
C2 - 12110000
AN - SCOPUS:0035991408
SN - 0085-2538
VL - 62
SP - 392
EP - 400
JO - Kidney International
JF - Kidney International
IS - 2
ER -