A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report

Frontiers in Neuroscience

Edouard Bardou-Jacquet¹  Martine Ropert²  Stéphane Durupt³  Sabine Mainbourg⁴  Claire Savy-Stortz⁷  Quitterie Reynaud⁸  Hervé Lobbes⁹ 

[1] 0INSERM, CIC141, CHU de Rennes, Rennes, France;Department of Biochemistry, CHU de Rennes, Rennes, France;Département de Médecine Interne et Centre de Référence Mucoviscidose, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France;Equipe Evaluation et Modélisation des Effets Thérapeutiques, UMR 5558, Laboratoire de Biométrie et Biologie évolutive, CNRS, Université Claude Bernard Lyon 1, Villeurbanne, France;INSERM, University of Rennes, INRAE, UMR 1241, AEM2 Platform, Nutrition Metabolisms and Cancer (NuMeCan) Institute, Rennes, France;Liver Disease Department, French Reference Center for Hemochromatosis and Iron Metabolism Disease, CHU de Rennes, Rennes, France;Médecine interne et médecine vasculaire, Groupe Hospitalier les Portes du Sud, Vénissieux, France;Research on Healthcare Performance (REHSAPE), INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France;SIGMA Clermont, Institut Pascal, CHU Clermont-Ferrand, Université Clermont Auvergne, CNRS, Clermont-Ferrand, France;Service de Médecine Interne, Hôpital Estaing, CHU de Clermont-Ferrand, Clermont-Ferrand, France;

关键词: aceruloplasminemia;    ferroxidase;    iron overload;    neurodegenerative disease;    genetic variation;   

DOI  :  10.3389/fnins.2022.906360

来源: DOAJ

【 摘 要 】

Aceruloplasminemia is a rare autosomal recessive inherited disorder. Mutations in the ceruloplasmin gene cause depressed ferroxidase activity leading to iron accumulation. The clinical phenotype is highly variable: anemia, retinopathy, diabetes mellitus, psychiatric disorders, and neurological symptoms including parkinsonian disorders and dementia are the main features of this disease. Characterized by high serum ferritin with low transferrin saturation, aceruloplasminemia uniquely combines brain, liver and systemic iron overload. We report here four new cases of aceruloplasminemia in a consanguineous North-African family. Genetic sequencing revealed a homozygous missense variant c.656T>A in exon 4 of the ceruloplasmin gene, which had been described previously as of “unknown significance” in the dbSNP database and never associated with ACP in the HGMD database. Ferroxidase activity was strongly depressed. Clinical manifestations varied among cases. The proband exhibited mild microcytic anemia, diabetes mellitus, psychosis and parkinsonism, whereas the other cases were asymptomatic or mildly anemic, although high serum ferritin and brain iron deposition were documented in all of them. Therapeutic management was complex. The proband started deferoxamine treatment when already symptomatic and he rapidly declined. In the asymptomatic cases, the treatment was associated with poor tolerance and was discontinued due to anemia requiring red blood cell transfusion. Our series illustrates the need for new therapeutic approaches to aceruloplasminemia.

【 授权许可】

Unknown