Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II
Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II
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DOI：
10.1046/j.1523-1755.2002.00468.x
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发表时间：
2002-08-01
影响因子：
19.6
通讯作者：
Milliner, DS
中科院分区：
文献类型：
--
作者：
Monico, CG;Persson, M;Milliner, DS
背景：高草酸尿症可能是特发性、继发性或由原发性高草酸尿症(PH)引起的。肝丙氨酸：乙醛酸氨基转移酶(AGT)或乙醛/羟基丙酮酸还原酶(GR/HPR)缺乏分别导致PHI或PHII。肝脏乙醇酸氧化酶(GO)是第三种遗传性高草酸尿症的候选酶。方法：6例儿童确诊为明显高草酸尿症、尿石症，肝脏AGT(N=5)和GR/HPR(N=4)正常。HPR低于正常，GR未测到一例。在一对受影响的同胞中，只有一人接受了活组织检查。进行GO突变筛查，并用[(13)C-2]草酸测定膳食草酸(OX)、肠道草酸吸收(EOA)、肾清除量(GFR)、部分草酸排泄量(FEox)和一级亲属尿草酸(FDR)，以了解高草酸尿的病因。结果：平均发病年龄19.2个月，尿草酸1.3+/-0.5 mmol/1.73 m(2)/24 h(Mean+/-SD)。检测到两个GO序列改变(T754C、IVS3-49C>；G)，与高草酸尿症无关。日粮(OX)为42+/-31 mg/d。EOA为9.4+/-3.6%，而对照组为7.6+/-1.2%(P=0.33)。GFR为90+/-19mL/min/1.73m(2)，FEOX4.2+/-1.4。除兄弟二人外，FDR患者中未发现高草酸尿。结论：这些患者表现为一种新的高草酸尿症和尿石症，无过量饮食(OX)、肠道高吸收或肝脏AGT、GR/HPR缺乏。草酸合成途径的改变，在肝脏或肾脏，或在肾小管草酸处理中是可能的解释。这对受影响的兄弟姐妹表明这是一种遗传基础。
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 [(13) C-2] 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 m(2) /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 m(2) 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 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.