Genetic and clinical heterogeneity in thirteen new cases with aceruloplasminemia. Atypical anemia as a clue for an early diagnosis
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
Publication date
2020ISSN
1422-0067
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
616.8 - Neurology. Neuropathology. Nervous system
Keywords
Aceruloplasminèmia
Ceruloplasmina
Metabolisme del ferro
Malaltia neurodegenerativa
Anèmia
Ferritina
Aceruloplasminemia
Ceruloplasmina
Metabolismo del hierro
Enfermedad neurodegenerativa
Anemia
Ferritina
Aceruloplasminemia
Ceruloplasmin
Iron metabolism
Neurodegenerative disease
Anemia
Ferritin
Pages
14
Publisher
MDPI
Collection
21; 7
Is part of
International Journal of Molecular Sciences
Citation
Vila Cuenca, Marc; Marchi, Giacomo; Barqué, Anna [et al.]. Genetic and clinical heterogeneity in thirteen new cases with aceruloplasminemia. Atypical anemia as a clue for an early diagnosis. International Journal of Molecular Sciences, 2020, 21(7), 2374. Disponible en: <https://www.mdpi.com/1422-0067/21/7/2374>. Fecha de acceso: 18 ene. 2022. DOI: 10.3390/ijms21072374
This item appears in the following Collection(s)
- Ciències de la Salut [740]
Rights
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/