Atypical variant of Alexander's disease with involvement of the spinal cord

Abstract

Alexander's disease is a leukoencephalopathy caused by mutations of the glial fibrillary acidic protein. In MRI extensive symmetrical signal changes of the frontal white matter are typical. Recently unusual variants of Alexander's disease involving the brain stem have been reported. We present a female patient with Alexander's disease. In her DNA a heterozygous missense mutation/variation c.205G>A: p.Glu69Lys in exon 1 of the GFAP gene was detected. Although highly likely, it is not proven that the variant is pathogenic, since it was not tested if the mutation arise de novo (DNA of parents not available). She presented to our department at the age of 7 years with a 2 year history of progressive vomiting, constipation, bladder dysfunction and gait abnormalities. On clinical examination she exhibited proximal muscle weakness, ataxic gait and nasal speech. MRI showed extensive supra- and infratentorial bilateral signal abnormality as well as swelling of the entire conus medullaris. Lumbar puncture revealed dysfunction of the blood brain barrier. Initially an inflammatory disorder was suspected and she was treated with steroids leading to an improvement of the clinical symptoms and regression of the oedema on control MRI. Up to now the clinical symptoms and the MRI findings are stable for six months.