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P 857. Unusual Presentation of Three Children with Alexander’s Disease and Therapy with Steroids
30 October 2018 (online)
Background: M. Alexander is an autosomal dominant hereditary leukodystrophy due to a mutation in the GFAP gene. Leading symptoms are a secondary macrocephaly, an increasing bilateral spastic cerebral palsy or primarily bulbar symptoms. Here, we describe three unusual presentations of Alexander’s disease and treatment response to steroids in two patients.
Patient 1: A 12-year-old patient presented with recurrent vomiting and weight loss. Initial therapy with omeprazole in the first hospital was not relieving the symptoms. A cerebral magnetic resonance imaging (MRI) study showed a T2 signal increase with contrast agent enrichment in the area postrema of the brain stem. Sequencing of the GFAP gene revealed a mutation in exon 1 (C. 26c > T, P. (Arg88Cys). After oral prednisolone was started followed by a maintenance therapy (7.5 mg every second day) she had a remarkable improvement of her symptoms.
Patient 2: 4 years and 6-months-old patient, who presented at 7 months an intention tremor in his hands. Brain MRI showed a leukodystrophy mainly in the subcortical frontal areas. A homozygous mutation was found in the exon 6 of the GFAP gene. During the second year of life, a severe dysphagia, refusal of food intake, and weight loss occurred. In the third year of life, her expressive language was severely impaired. The cMRI showed progress in the brain stem with contrast agent enrichment. Steroid treatment did lead to partial improvement of symptoms.
Patient 3: A 13-month-old patient had at 3 months of age focal seizures. cMRI showed a leukodystrophy with symmetrical signal changes arising in area of the central white matter regions. A mutation in the GFAP gene (c. 230A > G, p. Asn77 ser) confirmed the diagnosis.
Summary: Children with M. Alexander show a wide range of neurological symptoms and can benefit from steroid treatment, in particular, in the context of brain stem involvement.