Nielsen Signe Marie Borch, Vinther-Jensen Tua, Nielsen Jørgen E, Nørremølle Anne, Hasholt Lis, Hjermind Lena E, Josefsen Knud
Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; The Bartholin Institute, Rigshospitalet, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark; Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Section 6922, Blegdamsvej 9, Copenhagen, DK-2100, Denmark.
J Neurol Sci. 2016 Mar 15;362:326-32. doi: 10.1016/j.jns.2016.02.018. Epub 2016 Feb 9.
Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study.
亨廷顿舞蹈症（HD）是一种由亨廷顿基因中CAG重复序列延长导致的常染色体显性遗传、进行性神经疾病。除了运动、精神和认知功能障碍外，还可见以代谢变化和细胞功能障碍形式出现的外周疾病表现。已对HD患者多种激素、代谢物和蛋白质的血液水平进行了分析，确定了一些与该疾病相关的变化。然而，尚未进行全面的肝功能测试（LFT）。我们使用临床应用的LFT面板，对一组有症状和无症状的HD基因扩展携带者及对照进行了研究。在此，我们证明，与无症状的HD基因扩展携带者相比，有症状的HD基因扩展携带者碱性磷酸酶水平升高，且与统一亨廷顿疾病评定量表-总功能能力评分（UHDRS-TFC）所表明的疾病严重程度增加相关。对于γ-谷氨酰转移酶，有症状组的升高水平比HD基因扩展阴性对照和无症状HD基因扩展携带者更常见。最后，与无症状的HD基因扩展携带者相比，有症状的HD基因扩展携带者总胆固醇和血糖适度升高，且与HD基因扩展阴性对照相比，C反应蛋白增加。我们的结果表明，与无症状的HD基因扩展携带者及对照相比，有症状者的LFT值升高更为频繁。大多数有症状的HD基因扩展携带者正在接受药物治疗，这可能会影响本研究中所进行的肝功能测试。
