Phenotype and molecular characterization of Wilson's disease in Morocco.

Autor: Abbassi N; Université Cadi Ayyad, Faculté des Sciences Semlalia, LHEAC, 40000, Marrakech, Morocco; Université Claude Bernard Lyon 1, INSERM-U1060, INRA, INSA, Laboratoire CarMeN, 69500, Lyon, France. Electronic address: nadiaabbassi3@gmail.com., Bourrahouat A; Université Cadi Ayyad, Faculté de Médecine et de pharmacie, Laboratoire de recherche de l'enfance, la santé et le développement, 40000, Marrakech, Morocco; CHU Mohammed VI de Marrakech, Hôpital Mère-Enfant, Service de Pédiatrie, 40080, Marrakech, Morocco., Bedoya EC; HCL, Centre de référence de la maladie de Wilson, 69500, Lyon, France; HCL, Hôpital Mère-Femme-Enfant, Unité de Gastroentrologie, Hépatologie et Nutrition, 69500, Lyon, France., Pagan C; HCL, Centre de Biochimie et Biologie Moléculaire, LBMMS, 69500, Lyon, France., Qabli ME; Université Cadi Ayyad, Faculté de Médecine et de pharmacie, Laboratoire de recherche de l'enfance, la santé et le développement, 40000, Marrakech, Morocco., Maidoumi S; Université Cadi Ayyad, Faculté des Sciences Semlalia, LHEAC, 40000, Marrakech, Morocco., Belmalih A; HCL, Centre de référence de la maladie de Wilson, 69500, Lyon, France., Guillaud O; HCL, Hôpital Mère-Femme-Enfant, Unité de Gastroentrologie, Hépatologie et Nutrition, 69500, Lyon, France., Kissani N; CHU Mohammed VI de Marrakech, Hôpital Arrazi, Service de Neurologie, 40080, Marrakech, Morocco., Abkari A; CHU Ibn Rochd de Casablanca, Hôpital Mère-Enfant, Service de Gastro-Pédiatrie, 20360, Casablanca, Morocco., Chahid I; CHU Ibn Rochd de Casablanca, Hôpital Mère-Enfant, Service de Gastro-Pédiatrie, 20360, Casablanca, Morocco., Rafai MA; CHU Ibn Rochd de Casablanca, Service de Neurologie adulte, 20360, Casablanca, Morocco., Mouane N; CHU Ibn Sina de Rabat, Hôpital Mère-Enfant, Service de Gastro-Pédiatrie, 10100, Rabat, Morocco., Kriouile Y; CHU Ibn Sina de Rabat, Hôpital Mère-Enfant, Service de Gastro-Pédiatrie, 10100, Rabat, Morocco., Aidi S; CHU Ibn Sina de Rabat, Service de Neurologie adulte, 10100 Rabat, Morocco., Hida M; CHU Hassan II de Fès, Hôpital Mère-Enfant, Service de Pédiatrie, 30050 Fès, Morocco., Idrissi ML; CHU Hassan II de Fès, Hôpital Mère-Enfant, Service de Pédiatrie, 30050 Fès, Morocco., Belahsen MF; CHU Hassan II de Fès, Service de Neurologie adulte, 30050, Fès, Morocco., Abkari ME; CHU Hassan II de Fès, Service de Gastroenterologie et Hépatologie adulte, 30050 Fès, Morocco., Rkain M; CHU Mohammed VI d'Oujda, Hôpital Mère-Enfant, Service de Pédiatrie, 60049 Oujda, Morocco., Ismaili Z; CHU Mohammed VI d'Oujda, Service de Gastroenterologie et Hépatologie adulte, 60049, Oujda, Morocco., Sedki A; Université Cadi Ayyad, Faculté des Sciences Semlalia, LHEAC, 40000, Marrakech, Morocco., Bost M; HCL, Centre de référence de la maladie de Wilson, 69500, Lyon, France; HCL, Centre de Biochimie et Biologie Moléculaire, LBMMS, 69500, Lyon, France., Aboussair N; Université Cadi Ayyad, Faculté de Médecine et de pharmacie, Laboratoire de recherche de l'enfance, la santé et le développement, 40000, Marrakech, Morocco; CHU Mohammed VI de Marrakech, Centre de recherche clinique, Service de Génétique, 40080, Marrakech, Morocco., Lachaux A; HCL, Centre de référence de la maladie de Wilson, 69500, Lyon, France; HCL, Hôpital Mère-Femme-Enfant, Unité de Gastroentrologie, Hépatologie et Nutrition, 69500, Lyon, France; Université Claude Bernard Lyon 1, CIRI-INSERM-U1111, CNRS UMR5308, 69100, Lyon, France.
Jazyk: angličtina
Zdroj: Clinics and research in hepatology and gastroenterology [Clin Res Hepatol Gastroenterol] 2024 May; Vol. 48 (5), pp. 102335. Date of Electronic Publication: 2024 Apr 06.
DOI: 10.1016/j.clinre.2024.102335
Abstrakt: Background and Study Aims: In Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients.
Patients and Methods: We collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters. The genotype was characterized in 18 families diagnosed at the University Hospital Center of Marrakesh, by next generation sequencing.
Results: The mean annual prevalence in Morocco was 3.88 per 100,000 and the allele frequency was 0.15 %. Among the 226 patients included (121 males and 105 females), 196 were referred for a hepatic or neurological involvement and 30 were asymptomatic. The mean age at diagnosis was 13 ± 5.1 years (range: 5 - 42 years). Consanguinity was found in 63.3 % of patients. The mean duration of illness was 2.8 ± 1.9 years. Kayser-Fleischer rings were found in 131 (67.9 %) of 193 patients. Among the 196 symptomatic patients, 141/159 (88.7 %) had low serum ceruloplasmin (<0.2 g/L) and a high 24-hours urinary copper (>100 μg/day) was found in 173/182 (95.1 %) patients. The initial treatment was D-penicillamine in 207 patients, zinc acetate in five, zinc sulfate in five, and nine patients were not treated; 60/207 (29 %) patients have stopped treatment. A total of 72 patients died; the mortality rate was 31.9 %. Eight different ATP7B variants were identified among the 18 patients studied, of which two were novel (p.Cys1104Arg and p.Gln1277Hisfs*52), and six previously published (p.Gln289Ter, p.Cys305Ter, p.Thr1232Pro, p.Lys1020Arg, p.Glu583ArgfsTer25 and c.51+4A>T). All informative patients were homozygous for the disease-causing mutation.
Conclusion: In Morocco, a high prevalence due to consanguinity and a high mortality rate due to the difficulty of diagnosis and lack of treatment were observed in WD patients. NGS sequencing identified new ATP7B variants in WD patients from Morocco.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by the Association pour le Développement de la Neurogénétique.
(Copyright © 2024. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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