Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis
Vila Cuenca, Marc (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Marchi, Giacomo (Azienda Ospedaliera Universitaria Integrata di Verona)
Barqué, Anna (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Esteban-Jurado, Clara (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Marchetto, Alessandro (University of Verona)
Giorgetti, Alejandro (Department of Biotechnology, University of Verona)
Chelban, Viorica (National Hospital for Neurology and Neurosurgery, London)
Houlden, Henry (National Hospital for Neurology and Neurosurgery, London)
Wood, Nicholas W.. (National Hospital for Neurology and Neurosurgery, London)
Piubelli, Chiara (Centre for Tropical Diseases, Ospedale Sacro Cuore - Don Calabria)
Dorigatti Borges, Marina (University of Campinas-UNICAMP)
Martins de Albuquerque, Dulcinéia (University of Campinas-UNICAMP)
Yotsumoto Fertrin, Kleber (University of Campinas-UNICAMP)
Jové-Buxeda, Ester (Universitat Autònoma de Barcelona. Departament de Medicina)
Sánchez-Delgado, Jordi (Universitat Autònoma de Barcelona. Departament de Medicina)
Baena Díez, Neus (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Burnyte, Birute (Vilnius University)
Utkus, Algirdas (Vilnius University)
Busti, Fabiana (Azienda Ospedaliera Universitaria Integrata di Verona)
Kaubrys, Gintaras (Vilnius University)
Suku, Eda (University of Verona)
Kowalczyk, Kamil (Medical University of Gdańsk)
Karaszewski, Bartosz (Medical University of Gdańsk)
Porter, John B. (University College London NHS Foundation Trust)
Pollard, Sally (Consultant Paediatrician, Bradford Royal Infirmary)
Eleftheriou, Perla (University College London NHS Foundation Trust)
Bignell, Patricia (Oxford University Hospitals NHS Foundation Trust)
Girelli, Domenico (Azienda Ospedaliera Universitaria Integrata di Verona)
Sánchez-Fernández, Mayka (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Date:	2020
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aceruloplasminemia ; Ceruloplasmin ; Iron metabolism ; Neurodegenerative disease ; Anemia ; Ferritin
Published in:	International journal of molecular sciences, Vol. 21 (march 2020) , ISSN 1422-0067

DOI: 10.3390/ijms21072374
PMID: 32235485

14 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles