Association Between Rapid Progression, Early Mortality, and Imaging in Neonatal-Onset Alexander Disease

Area of Science:

• Neuroscience
• Genetics
• Pediatric Neurology

Background:

• Alexander disease is a rare genetic leukodystrophy characterized by abnormal astrocytic inclusions.
• Neonatal onset is associated with variable survival, potentially linked to mutation type and protein accumulation.
• Glial fibrillary acidic protein (GFAP) mutations are a primary cause.

Purpose of the Study:

• To describe the clinical and imaging features of a neonatal Alexander disease case.
• To investigate the genotype-phenotype correlation in neonatal Alexander disease.
• To evaluate the utility of serial cranial ultrasound in monitoring disease progression.

Main Methods:

• Case study of a female newborn with neonatal-onset Alexander disease.
• Genetic analysis identifying a de novo GFAP mutation (c.1106T>C; p.(Leu369Pro)).
• Serial magnetic resonance imaging (MRI) and cranial ultrasound (cUS) for monitoring brain abnormalities.

Main Results:

• The patient presented with early seizures, lethargy, and rapid deterioration.
• Brain imaging revealed rapidly evolving abnormalities, consistent with GFAP accumulation.
• The specific GFAP mutation (c.1106T>C) was associated with early death.
• High-resolution ultrasound proved effective for serial bedside monitoring.

Conclusions:

• Neonatal Alexander disease with the c.1106T>C GFAP mutation shows a poor prognosis with rapid clinical decline.
• Early onset seizures and rapid deterioration indicate a severe phenotype.
• Serial cranial ultrasound is a valuable tool for managing and monitoring neonatal Alexander disease.