title: Vanishing white matter disease in a spanish population.
abstract: Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor (eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5.
authors.affiliation: Neurology Department, Fundació, Hospital Sant Joan de Déu, Barcelona, Spain. ; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Turón-Viñas
authors.affiliation: Neurology Department, Fundació, Hospital Sant Joan de Déu, Barcelona, Spain. ; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Pineda
authors.affiliation: Pathology Department, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Victòria
authors.initials: V
authors.lastname: Cusí
authors.affiliation: Pediatric Neurology Unit, Department of Pediatrics, Reina Sofia University Hospital, Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Córdoba, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Laso
authors.affiliation: Neuropediatrics Unit, Hospital Infantil Niño Jesús, Madrid, Spain.
authors.forename: Rebeca Losada
authors.initials: RL
authors.lastname: Del Pozo
authors.affiliation: Neuropediatrics Unit, Hospital Infantil Niño Jesús, Madrid, Spain.
authors.forename: Luis González
authors.initials: LG
authors.lastname: Gutiérrez-Solana
authors.affiliation: Neuropediatrics Unit, Hospital Universitario de Burgos, Burgos, Spain.
authors.forename: David Conejo
authors.initials: DC
authors.lastname: Moreno
authors.affiliation: Neuropediatrics Unit, Hospital de Jaén, Jaén, Spain.
authors.forename: Concha
authors.initials: C
authors.lastname: Sierra-Córcoles
authors.affiliation: Neuropediatrics Unit, Hospital de Cruces, Barakaldo-Bizkaia, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Olabarrieta-Hoyos
authors.affiliation: Neuropediatrics Section, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Madruga-Garrido
authors.affiliation: Neuropediatrics Unit, Hospital de Torrecárdenas, Almería, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Aguirre-Rodríguez
authors.affiliation: Neurology Department, Fundació, Hospital Sant Joan de Déu, Barcelona, Spain. ; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: González-Álvarez
authors.affiliation: Neurology Department, Fundació, Hospital Sant Joan de Déu, Barcelona, Spain. ; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: O'Callaghan
authors.affiliation: Neurology Department, Fundació, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Muchart
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Spain. ; Molecular Genetics Department, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Armstrong-Moron
keywords: Spain; children; genetics; leukodystrophy; pathology; vanishing white matter disease
references.citation: J Neuropathol Exp Neurol. 2010 Oct;69(10):987-96
references.pmid: 20838246
references.citation: Clin Chem. 2005 Nov;51(11):2031-42
references.pmid: 16155092
references.citation: Neuropediatrics. 2008 Feb;39(1):29-32
references.pmid: 18504679
references.citation: Ment Retard Dev Disabil Res Rev. 2006;12(2):123-8
references.pmid: 16807905
references.citation: Eur Radiol. 2005 Nov;15(11):2377-9
references.pmid: 15856236
references.citation: Neurology. 1997 Apr;48(4):845-55
references.pmid: 9109866
references.citation: Eur J Neurol. 2009 Mar;16(3):e42-3
references.pmid: 19170749
references.citation: Neuropediatrics. 1993 Oct;24(5):244-8
references.pmid: 8309512
references.citation: Pediatr Neurol. 2006 Jul;35(1):65-8
references.pmid: 16814090
references.citation: J Child Neurol. 2011 Mar;26(3):366-8
references.pmid: 21115745
references.citation: Neurology. 2009 Feb 24;72(8):750-9
references.pmid: 19237705
references.citation: Neurology. 2004 May 11;62(9):1509-17
references.pmid: 15136673
references.citation: Mol Genet Metab. 2006 May;88(1):7-15
references.pmid: 16378743
references.citation: J Headache Pain. 2012 Nov;13(8):661-7
references.pmid: 23080079
references.citation: J Child Neurol. 2003 Sep;18(9):639-45
references.pmid: 14572143
references.citation: Rev Neurol. 2002 Jan 1-15;34(1):19-27
references.pmid: 11988888
references.citation: Neurology. 1995 Aug;45(8):1526-32
references.pmid: 7644053
references.citation: Ann Neurol. 1994 Mar;35(3):331-40
references.pmid: 8122885
references.citation: Lancet Neurol. 2006 May;5(5):413-23
references.pmid: 16632312
references.citation: J Child Neurol. 2008 Feb;23(2):205-15
references.pmid: 18263758
references.citation: Neurol Sci. 2006 Sep;27(4):271-7
references.pmid: 16998732
references.citation: Neurology. 1998 Aug;51(2):540-7
references.pmid: 9710032
references.citation: Eur J Paediatr Neurol. 2006 Jul;10(4):192-3
references.pmid: 16952472
references.citation: Ann Neurol. 2005 Oct;58(4):634-9
references.pmid: 16047349
references.citation: Top Magn Reson Imaging. 2006 Aug;17(4):219-42
references.pmid: 17414998
references.citation: Nat Genet. 2001 Dec;29(4):383-8
references.pmid: 11704758
references.citation: Neurology. 2002 Dec 24;59(12):1966-8
references.pmid: 12499492