Infantile and juvenile presentations of Alexander's disease: a report of two cases

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Alexander's disease is a rare, progressive, and often fatal genetic leukoencephalopathy characterized by demyelination and the accumulation of Rosenthal fibers (RFs) in the central nervous system.
• The disease typically presents in infancy or childhood, but adult-onset forms exist, presenting a diagnostic challenge.
• Understanding the genetic basis and pathological mechanisms is crucial for diagnosis and potential therapeutic strategies.

Observation:

• Two new cases of Alexander's disease are presented, marking the first reported instances in Belgium.
• Case 1: A 4-year-old girl with megalencephaly, intellectual disability, spastic tetraparesis, ataxia, and epilepsy, with post-mortem findings of widespread myelin loss and RFs.
• Case 2: A 10-year-old with progressive spastic paraparesis, palatal myoclonus, nystagmus, and spinal deformities, with biopsy confirming numerous RFs and radiological evidence of anterior leukoencephalopathy.

Findings:

• The cases illustrate the diverse clinical manifestations and pathological hallmarks of Alexander's disease across different age groups.
• Post-mortem and biopsy findings confirm the presence of widespread myelin loss and Rosenthal fibers, consistent with Alexander's disease.
• The review of literature and discussion of nosology and pathogenesis provide a comprehensive overview of the condition.

Implications:

• These cases expand the geographical reporting of Alexander's disease and contribute to the understanding of its clinical spectrum.
• The study emphasizes the importance of recognizing specific clinical and radiological clues for early diagnosis in living patients.
• Further research into the pathogeny of RFs and dysmyelination may offer insights into therapeutic targets for Alexander's disease.