Robertson K J, Clarke D, Sutherland L, Wooster R, Coughtrie M W, Burchell B
Department of Biochemical Medicine, Ninewells Hospital and Medical School, University of Dundee, UK.
J Inherit Metab Dis. 1991;14(4):563-79. doi: 10.1007/BF01797927.
Liver biopsy samples were obtained from eight Crigler-Najjar patients. Bilirubin UDPGT activity, assayed by a microassay with HPLC analysis, was not detectable in type I livers, and low levels (9-26% of controls) of monoglucuronide conjugates only were observed in type II livers. 1-Naphthol UDPGT activity was normal in most patients, where membrane integrity was maintained by correct sample procurement and preparation. Our data on type II livers suggest that a defect in UDPGA transport is an unlikely cause of the hyperbilirubinaemia, but reduced affinity for UDPGA was observed in one sample. Analysis of four patient liver samples by immunoblot analysis revealed the heterogeneous nature of this inherited disease within the patient population, and one sample where 1-naphthol UDPGT activity was considerably reduced appeared to correlate with the non-detection of a phenol UDPGT protein. Progress towards a molecular genetic diagnosis of Crigler-Najjar syndromes is discussed.
从8名克里格勒 - 纳贾尔综合征患者身上获取了肝脏活检样本。通过高效液相色谱分析的微量测定法检测，I型肝脏中未检测到胆红素UDPGT活性，而在II型肝脏中仅观察到低水平（对照组的9 - 26%）的单葡萄糖醛酸酯结合物。在大多数通过正确的样本采集和制备维持膜完整性的患者中，1 - 萘酚UDPGT活性正常。我们关于II型肝脏的数据表明，UDPGA转运缺陷不太可能是高胆红素血症的原因，但在一个样本中观察到对UDPGA的亲和力降低。通过免疫印迹分析对4例患者肝脏样本进行分析，揭示了该遗传性疾病在患者群体中的异质性，并且1 - 萘酚UDPGT活性显著降低的一个样本似乎与未检测到酚UDPGT蛋白相关。讨论了克里格勒 - 纳贾尔综合征分子遗传学诊断的进展。
