Atypical presentation of infantile Alexander disease without macrocephaly

Abstract Background Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age, and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. Case report An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegaly. The widespread hypodense white matter was found on magnetic resonance, and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and sequencing of GALC gene. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G > A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). Conclusions The neuroradiology signs observed in the resonance were decisive for the diagnosis later confirmed by molecular techniques. It is important to consider that certain mutations are not associated with macrocephaly, which may cause a delay in the diagnosis.