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Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis
Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178074/ https://www.ncbi.nlm.nih.gov/pubmed/32235485 http://dx.doi.org/10.3390/ijms21072374 |
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author | Vila Cuenca, Marc Marchi, Giacomo Barqué, Anna Esteban-Jurado, Clara Marchetto, Alessandro Giorgetti, Alejandro Chelban, Viorica Houlden, Henry Wood, Nicholas W Piubelli, Chiara Dorigatti Borges, Marina Martins de Albuquerque, Dulcinéia Yotsumoto Fertrin, Kleber Jové-Buxeda, Ester Sanchez-Delgado, Jordi Baena-Díez, Neus Burnyte, Birute Utkus, Algirdas Busti, Fabiana Kaubrys, Gintaras Suku, Eda Kowalczyk, Kamil Karaszewski, Bartosz Porter, John B. Pollard, Sally Eleftheriou, Perla Bignell, Patricia Girelli, Domenico Sanchez, Mayka |
author_facet | Vila Cuenca, Marc Marchi, Giacomo Barqué, Anna Esteban-Jurado, Clara Marchetto, Alessandro Giorgetti, Alejandro Chelban, Viorica Houlden, Henry Wood, Nicholas W Piubelli, Chiara Dorigatti Borges, Marina Martins de Albuquerque, Dulcinéia Yotsumoto Fertrin, Kleber Jové-Buxeda, Ester Sanchez-Delgado, Jordi Baena-Díez, Neus Burnyte, Birute Utkus, Algirdas Busti, Fabiana Kaubrys, Gintaras Suku, Eda Kowalczyk, Kamil Karaszewski, Bartosz Porter, John B. Pollard, Sally Eleftheriou, Perla Bignell, Patricia Girelli, Domenico Sanchez, Mayka |
author_sort | Vila Cuenca, Marc |
collection | PubMed |
description | Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmin (CP) gene that produce a strong reduction or absence of ceruloplasmin ferroxidase activity, leading to an impairment of iron metabolism. Most patients described so far are from Japan. Prompt diagnosis and therapy are crucial to prevent neurological complications since, once established, they are usually irreversible. Here, we describe the largest series of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene (7 missense, 3 frameshifts, and 3 splicing mutations), 10 of which are novel. All missense mutations were studied by computational modeling. Clinical manifestations were heterogeneous, but anemia, often but not necessarily microcytic, was frequently the earliest one. This study confirms the clinical and genetic heterogeneity of aceruloplasminemia, a disease expected to be increasingly diagnosed in the Next-Generation Sequencing (NGS) era. Unexplained anemia with low transferrin saturation and high ferritin levels without inflammation should prompt the suspicion of aceruloplasminemia, which can be easily confirmed by low serum ceruloplasmin levels. Collaborative joint efforts are needed to better understand the pathophysiology of this potentially disabling disease. |
format | Online Article Text |
id | pubmed-7178074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71780742020-04-28 Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis Vila Cuenca, Marc Marchi, Giacomo Barqué, Anna Esteban-Jurado, Clara Marchetto, Alessandro Giorgetti, Alejandro Chelban, Viorica Houlden, Henry Wood, Nicholas W Piubelli, Chiara Dorigatti Borges, Marina Martins de Albuquerque, Dulcinéia Yotsumoto Fertrin, Kleber Jové-Buxeda, Ester Sanchez-Delgado, Jordi Baena-Díez, Neus Burnyte, Birute Utkus, Algirdas Busti, Fabiana Kaubrys, Gintaras Suku, Eda Kowalczyk, Kamil Karaszewski, Bartosz Porter, John B. Pollard, Sally Eleftheriou, Perla Bignell, Patricia Girelli, Domenico Sanchez, Mayka Int J Mol Sci Article Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmin (CP) gene that produce a strong reduction or absence of ceruloplasmin ferroxidase activity, leading to an impairment of iron metabolism. Most patients described so far are from Japan. Prompt diagnosis and therapy are crucial to prevent neurological complications since, once established, they are usually irreversible. Here, we describe the largest series of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene (7 missense, 3 frameshifts, and 3 splicing mutations), 10 of which are novel. All missense mutations were studied by computational modeling. Clinical manifestations were heterogeneous, but anemia, often but not necessarily microcytic, was frequently the earliest one. This study confirms the clinical and genetic heterogeneity of aceruloplasminemia, a disease expected to be increasingly diagnosed in the Next-Generation Sequencing (NGS) era. Unexplained anemia with low transferrin saturation and high ferritin levels without inflammation should prompt the suspicion of aceruloplasminemia, which can be easily confirmed by low serum ceruloplasmin levels. Collaborative joint efforts are needed to better understand the pathophysiology of this potentially disabling disease. MDPI 2020-03-30 /pmc/articles/PMC7178074/ /pubmed/32235485 http://dx.doi.org/10.3390/ijms21072374 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vila Cuenca, Marc Marchi, Giacomo Barqué, Anna Esteban-Jurado, Clara Marchetto, Alessandro Giorgetti, Alejandro Chelban, Viorica Houlden, Henry Wood, Nicholas W Piubelli, Chiara Dorigatti Borges, Marina Martins de Albuquerque, Dulcinéia Yotsumoto Fertrin, Kleber Jové-Buxeda, Ester Sanchez-Delgado, Jordi Baena-Díez, Neus Burnyte, Birute Utkus, Algirdas Busti, Fabiana Kaubrys, Gintaras Suku, Eda Kowalczyk, Kamil Karaszewski, Bartosz Porter, John B. Pollard, Sally Eleftheriou, Perla Bignell, Patricia Girelli, Domenico Sanchez, Mayka Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis |
title | Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis |
title_full | Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis |
title_fullStr | Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis |
title_full_unstemmed | Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis |
title_short | Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis |
title_sort | genetic and clinical heterogeneity in thirteen new cases with aceruloplasminemia. atypical anemia as a clue for an early diagnosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178074/ https://www.ncbi.nlm.nih.gov/pubmed/32235485 http://dx.doi.org/10.3390/ijms21072374 |
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