与母乳和胆红素尿苷二磷酸-葡萄糖醛酸转移酶基因突变相关的长时间非偶联高胆红素血症。
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Maruo Y, Nishizawa K, Sato H, Sawa H，岛田M
与母乳和胆红素尿苷二磷酸-葡萄糖醛酸转移酶基因突变相关的长时间非偶联高胆红素血症。
儿科学。2000年11月;106(5):E59。
- PubMed ID
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11061796 (PubMed视图］
- 摘要
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目的:母乳黄疸是哺乳婴儿的常见问题。它被归因于各种母乳物质，但成分或成分的组合仍不清楚。在我们对遗传性未结合高胆红素血症(crigbler - najjar综合征和Gilbert综合征)和新生儿高胆红素血症患者胆红素尿苷二磷酸葡萄糖醛酸转移酶基因(UGT1A1)缺陷的研究中，我们遇到了一个与母乳喂养相关的长时间病例;停止母乳喂养后，婴儿的胆红素水平恢复正常。基因分析显示了一种与吉尔伯特综合征患者相同的错义突变，通常在青春期后导致黄疸。我们分析了与母乳相关的长时间非结合性高胆红素血症婴儿的胆红素UGT1A1，以确定是否涉及遗传因素。患者和方法:我们分析了出生后3周至1个月的17例明显延长黄疸的母乳喂养的日本婴儿(总血清胆红素浓度高于171微mol/L [10 mg/dL])。除了黄疸，婴儿都很健康，没有溶血性贫血、肝功能障碍或甲状腺功能减退的迹象。停止母乳喂养后，所有病例的血清胆红素浓度开始下降。恢复母乳喂养后，一些婴儿的血清胆红素浓度再次升高，但到4个月大时浓度降至正常范围。 We analyzed the polymerase chain reaction-amplified exon, promoter, and enhancer regions of UGT1A1 by direct sequencing. RESULTS: Sixteen infants had at least one mutation of the UGT1A1. Seven were homozygous for 211G-->A (G71R), which is the most common mutation detected in the East Asian population, and the mutant enzyme had one third of the normal activity. G71R is the most common missense mutation we found in our analyses in Japanese patients with Gilbert's syndrome, and it corresponds to a UGT1A1 polymorphism in the Japanese population (the allele frequency is.16). One was heterozygous for 1456T-->G (Y486D) and homozygous for 211G-->A. Six were heterozygous for 211G-->A. One was heterozygous for both 211G-->A and a TATA box mutation (A(TA)7TAA). One had a heterozygous mutation in an enhancer region (C-->A at -1353). We did not detect a homozygous A(TA)7TAA mutation, which was the most common cause of Gilbert's syndrome in European population, in this study of Japanese infants with prolonged hyperbilirubinemia triggered by breast milk. CONCLUSIONS: The results indicate that defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. The mutations we found were identical to those detected in patients with Gilbert's syndrome, a risk factor of neonatal nonphysiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia.