Rapid Progression and Early Mortality in Neonatal-Onset Alexander Disease: Association between Clinical Deterioration, Cranial Ultrasound and Magnetic Resonance Imaging

Background Alexander disease represents a rare genetic leukodystrophy caused by abnormal astrocytic accumulations of intracytoplasmic proteinaceous inclusions with astrocyte dysfunction. With neonatal onset, survival ranges from 1.5 months to more than 7.5 years, with a possible association between the underlying point mutation, the level of protein accumulation in the cerebral white matter, disease progression, and survival time. Results We describe the clinical and cerebral imaging features of a female newborn with neonatal-onset Alexander disease caused by a heterozygous de novo point mutation c.1106T>C; p.(Leu369Pro) located in the coil 2B area of the glial fibrillary acidic protein (GFAP). Early-onset seizures, lethargy, and rapid loss of spontaneous movements were accompanied by rapidly evolving brain morphologic abnormalities and early death. The progression of cerebral abnormalities was monitored by MR imaging and serial cranial ultrasound exams. Conclusions As shown in this case study and accompanied literature review, rapid accumulation of GFAP, as indicated by volume expansion of affected structures on brain imaging, combined with early onset of seizures, and rapid clinical deterioration seems to be associated with poor prognosis. In this case high-resolution ultrasound offered an easy accessible, serial bedside imaging tool for the detection and follow-up of pathognomonic features of Alexander disease.