Neonatal cholestasis with increased3β-monohydroxy-Δ bile acids inserum and urine: not necessarilyprimary oxysterol7α hydroxylase deficiency.
Neonatal cholestasis with increased3β-monohydroxy-Δ bile acids inserum and urine: not necessarilyprimary oxysterol7α hydroxylase deficiency.
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新生儿胆汁淤积伴血清和尿液中 3β-单羟基-Δ 胆汁酸增加：不一定是原发性氧化甾醇 7α 羟化酶缺乏症。
DOI：
10.1016/j.cca.2012.05.016
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Takei H.
中科院分区：
文献类型：
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作者：
Kimura A;Nittono H;Mizuochi T,Ueki I;Kurosawa T;Muto A;Takei H.
背景胆汁酸合成先天性错误是一种罕见的遗传性疾病，可导致胆汁淤积性肝病。最近我们遇到了3例新生儿胆汁淤积症，血清和尿液中3β-单羟基-Δ5-C24bile酸过量。我们探讨在胆汁淤积症患者的血清和尿液中检测3β-羟基-5-胆固醇酸和27-羟基胆固醇是否对原发性氧甾醇7α-羟化酶缺乏症的诊断有必要。方法3例患者初步怀疑为氧甾醇7α-羟化酶缺乏症。然而，基因组DNA序列分析显示，2例患者诊断为氧甾醇7α-羟化酶缺乏症，1例患者诊断为3β-羟基-Δ5-C27-steroid脱氢酶/异构酶缺乏症。诊断后采用气相色谱-质谱法检测3β-羟基-5-胆固醇酸和27-羟基胆固醇。结果有趣的是，我们在2例诊断为原发性氧甾醇7α-羟化酶缺乏症的患者中检测到血清中3β-羟基-5-胆甾酸和尿中27-羟基胆固醇的峰值。结论评价婴幼儿胆汁淤积及3β-单羟基-Δ5-C24bile酸过量，需连续进行c24胆汁酸分析。结果可以指导基因组DNA分析的性能和解释。此外，血清中3 - β-羟基-5-胆甾酸和尿液中27-羟基胆固醇的鉴定对诊断氧甾醇7α-羟化酶缺乏症非常重要，基因组DNA分析也是如此。
BACKGROUNDInborn errors of bile acid synthesis are rare genetic disorders that can present with cholestatic liver disease. Recently we encountered 3 infants with neonatal cholestasis and excessive 3β-monohydroxy-Δ5-C24bile acids in serum and urine. We investigated whether identification of 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol in serum and urine of cholestatic patients is necessary for diagnosis of primary oxysterol 7α-hydroxylase deficiency.METHODSThese 3 patients initially led us to suspected oxysterol 7α-hydroxylase deficiency. However, sequence analysis of genomic DNA resulted in diagnosis of 2 patients with oxysterol 7α-hydroxylase deficiency and 1 patient with 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase deficiency. We examined identification of 3β-hydroxy-5-cholestenoic acid and 27-hydroxycholesterol by gas chromatography–mass spectrometry after diagnosis.RESULTSInterestingly, we detected a peak for 3β-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol of the neutral sterol in urine from 2 patients who were diagnosed with primary oxysterol 7α-hydroxylase deficiency.CONCLUSIONIn evaluating infants with cholestasis and excessive 3β-monohydroxy-Δ5-C24bile acids in infancy, one needs to conduct C24bile acid analysis serially. Results can guide performance and interpretation of genomic DNA analysis. Moreover, identification of 3β-hydroxy-5-cholestenoic acid in serum and 27-hydroxycholesterol in urine is highly important for diagnosis of oxysterol 7α-hydroxylase deficiency as is genomic DNA analysis.