Adult-onset Alexander Disease : Report on a Family

Overview

Journal J Neurol

Specialty Neurology

Date 2007 Nov 16

PMID 18004641

Citations 18

Authors

Pietro Balbi

Marco Seri

Isabella Ceccherini

Carla Uggetti

Roberto Casale

Cira Fundaro

Francesco Caroli

Lucio Santoro

Affiliations

Soon will be listed here.

Abstract

Pathogenic, dominant, de novo missense mutations in the glial fibrillary acidic protein (GFAP) have been found in the three subtypes of infantile, juvenile and adult Alexander disease. Here we describe four members of an Italian family (32 to 66-yearsold, 2 women and 2 men) affected by adult Alexander disease, the least common and the most clinically variable form. Direct sequencing of all coding regions of the GFAP gene, neurological examination and brain MRI were performed. Two novel missense mutations were found involving two very close codons, c.[988C > G, 994G > A], leading to p.[Arg330Gly, Glu332Lys]. Clinically, two members exhibited pseudo-bulbar signs, gait ataxia and spasticity, one showed a severe cranial sensory symptomatology, and one subject was asymptomatic.Medulla and cervical cord atrophy was present in all of them on MRI. Although adult Alexander disease shows a wide clinical variability, a more frequent pattern can be identified characterized by bulbar or pseudo-bulbar signs, gait ataxia, and spasticity, and including on MRI medulla and cervical cord atrophy. Our findings also confirm that the clinical spectrum of adult Alexander disease includes cases without overt neurological involvement and with minimal brain MRI alterations.

Citing Articles

External Laryngeal Tremor in Adult-Onset Alexander Disease: A Case Report.

Gazulla J, Rodriguez-Valle A, Calatayud-Lallana L, Berciano J Case Rep Neurol. 2024; 16(1):129-135.

PMID: 39015829 PMC: 11249790. DOI: 10.1159/000539038.

Substitution of Glu to Lys at Codon 332 on the GFAP Gene Alone Is Causative for Adult-onset Alexander Disease.

Sanjo N, Suzuki M, Yoshihama R, Toyoshima Y, Mizuta I, Fujita N Intern Med. 2023; 63(2):309-313.

PMID: 37197954 PMC: 10864087. DOI: 10.2169/internalmedicine.1726-23.

Identification of a novel de novo pathogenic variant in GFAP in an Iranian family with Alexander disease by whole-exome sequencing.

Heshmatzad K, Naderi N, Masoumi T, Pouraliakbar H, Kalayinia S Eur J Med Res. 2022; 27(1):174.

PMID: 36088400 PMC: 9464415. DOI: 10.1186/s40001-022-00799-5.

Does genetic anticipation occur in familial Alexander disease?.

Hunt C, Al Khleifat A, Burchill E, Ederle J, Al-Chalabi A, Sreedharan J Neurogenetics. 2021; 22(3):215-219.

PMID: 34046764 PMC: 8241638. DOI: 10.1007/s10048-021-00642-9.

Long-term survival of a dog with Alexander disease.

Kobatake Y, Nishimura N, Sakai H, Iwana S, Yamato O, Nishii N J Vet Med Sci. 2020; 82(11):1704-1707.

PMID: 33055453 PMC: 7719875. DOI: 10.1292/jvms.20-0133.

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