title: Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting.
abstract: 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.
authors.affiliation: 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. Electronic address: smborch@sund.ku.dk.
authors.forename: Signe Marie Borch
authors.initials: SM
authors.lastname: Nielsen
authors.affiliation: 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.
authors.forename: Tua
authors.initials: T
authors.lastname: Vinther-Jensen
authors.affiliation: 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.
authors.forename: Jørgen E
authors.initials: JE
authors.lastname: Nielsen
authors.affiliation: Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Nørremølle
authors.affiliation: Section of Neurogenetics, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
authors.forename: Lis
authors.initials: L
authors.lastname: Hasholt
authors.affiliation: 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.
authors.forename: Lena E
authors.initials: LE
authors.lastname: Hjermind
authors.affiliation: The Bartholin Institute, Rigshospitalet, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Knud
authors.initials: K
authors.lastname: Josefsen
mesh_terms: D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein; D003072:Cognition Disorders / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000097:blood* / Q000150:complications* / Q000235:genetics; D008107:Liver Diseases / Q000209:etiology* / Q000235:genetics; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D002097:C-Reactive Protein; D005723:gamma-Glutamyltransferase
keywords: Alkaline phosphatase; Gamma-glutamyl transferase; Hepatotoxicity; Huntington's disease; Liver; Liver function test