Atypical Presentation of Infantile Alexander Disease: A Case Report

Abstract

Introduction: Alexander disease is a rare autosomal dominant leukodystrophy that affects the white matter of the central nervous system (CNS), predominantly involving the bilateral frontal lobes. It is caused by mutations in the glial fibrillary acidic protein (GFAP) gene located on chromosome 17q21. Although it can occur at any age, the infantile form is typically characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia.

Case Report: A 4-year-old girl was evaluated after presenting with febrile status epilepticus. Physical examination revealed macrocephaly and pyramidal signs without spasticity. Computed tomography demonstrated diffuse hypodensity of the cerebral white matter, while magnetic resonance imaging (MRI) showed bilateral and symmetrical hyperintense white matter lesions. The neuroimaging findings, together with macrocephaly, raised suspicion of Alexander disease, which was confirmed by GFAP gene sequencing that identified a pathogenic c.231T>A mutation.

Conclusions: The characteristic MRI findings were crucial in establishing the diagnosis, which was subsequently confirmed by molecular genetic testing. Although the infantile form of Alexander disease usually presents with a characteristic clinical phenotype, atypical manifestations may delay diagnosis. Therefore, Alexander disease should be considered in the differential diagnosis of children presenting with macrocephaly and neurological manifestations.