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

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 sympt...

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Autores principales: Lobbes, Hervé, Reynaud, Quitterie, Mainbourg, Sabine, Savy-Stortz, Claire, Ropert, Martine, Bardou-Jacquet, Edouard, Durupt, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108494/
https://www.ncbi.nlm.nih.gov/pubmed/35585918
http://dx.doi.org/10.3389/fnins.2022.906360
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author Lobbes, Hervé
Reynaud, Quitterie
Mainbourg, Sabine
Savy-Stortz, Claire
Ropert, Martine
Bardou-Jacquet, Edouard
Durupt, Stéphane
author_facet Lobbes, Hervé
Reynaud, Quitterie
Mainbourg, Sabine
Savy-Stortz, Claire
Ropert, Martine
Bardou-Jacquet, Edouard
Durupt, Stéphane
author_sort Lobbes, Hervé
collection PubMed
description 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.
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spelling pubmed-91084942022-05-17 A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report Lobbes, Hervé Reynaud, Quitterie Mainbourg, Sabine Savy-Stortz, Claire Ropert, Martine Bardou-Jacquet, Edouard Durupt, Stéphane Front Neurosci Neuroscience 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. Frontiers Media S.A. 2022-05-02 /pmc/articles/PMC9108494/ /pubmed/35585918 http://dx.doi.org/10.3389/fnins.2022.906360 Text en Copyright © 2022 Lobbes, Reynaud, Mainbourg, Savy-Stortz, Ropert, Bardou-Jacquet and Durupt. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Lobbes, Hervé
Reynaud, Quitterie
Mainbourg, Sabine
Savy-Stortz, Claire
Ropert, Martine
Bardou-Jacquet, Edouard
Durupt, Stéphane
A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
title A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
title_full A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
title_fullStr A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
title_full_unstemmed A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
title_short A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report
title_sort new pathogenic missense variant in a consanguineous north-african family responsible for a highly variable aceruloplasminemia phenotype: a case-report
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108494/
https://www.ncbi.nlm.nih.gov/pubmed/35585918
http://dx.doi.org/10.3389/fnins.2022.906360
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