Adult-onset Alexander disease
- 243 Downloads
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.
Key wordsAlexander disease GFAP mutations neurodegenerative disorder signs and symptoms
Unable to display preview. Download preview PDF.
- 5.Caroli F, Biancheri R, Seri M, Rossi A, Pessagno A, Bugiani M, Corsolini F, Savasta S, Romano S, Antonelli C, Romano A, Pareyson D, Gambero P, Uziel G, Ravazzolo R, Ceccherini I, Filocamo M (2007) GFAP mutations and polymorphisms in 13 unrelated Italian patients affected by Alexander disease. Clin Genet 72(5):427–433PubMedCrossRefGoogle Scholar
- 8.Gorospe JR, Naidu S, Johnson AB, Puri V, Raymond GV, Jenkins SD, Pedersen RC, Lewis D, Knowles P, Fernandez R, De Vivi D, van der Knapp MS, Messing A, Brenner M, Hoffman EP (2002) Molecular findings in symptomatic and pre-simptomatic Alexander disease patients. Neurology 58:1494–1500PubMedGoogle Scholar
- 15.Li R, Johnson AB, Salomons G, Goldman JE, Naidu S, Quinlan R, Cree B, Ruyle SZ, Banwell B, D'Hooghe M, Siebert JR, Rolf CM, Cox H, Reddy A, González Gutiérrez-Solana L, Collins A, Weller RO, Messing A, van der Knaap M, Brenner M (2005) Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol 57(3):310–326PubMedCrossRefGoogle Scholar
- 20.Rosenthal W (1898) Über eine eigentümliche, mit Syringomyelie komplizierte Geschwulst des Rückenmarks. Beitr path Anat 23:111Google Scholar