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Infantile-onset Alexander disease: a genetically proven case with mild clinical course in a 6-year-old Indian boy

Konanki Ramesh1, Suvasini Sharma, Atin Kumar

  • 1Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India.

Journal of Child Neurology
|May 9, 2012
PubMed

Insights

Alexander disease, a rare brain disorder, typically causes developmental delays. This report details a unique case with a mild presentation linked to a new GFAP gene mutation.

Area of Science:

  • Neuroscience
  • Genetics
  • Pediatric Neurology

Background:

  • Alexander disease is a rare, fatal, autosomal dominant leukoencephalopathy.
  • It is characterized by progressive demyelination and gliosis, primarily affecting the white matter of the brain.
  • Clinical manifestations include macrocephaly, developmental delay, seizures, and spasticity, with a poor prognosis.

Observation:

  • A 6-year-old Indian boy presented with symptoms suggestive of infantile-onset Alexander disease.
  • The patient exhibited an unusually mild clinical course compared to typical presentations.
  • Neuroimaging revealed abnormalities predominantly in the frontal lobes, consistent with leukoencephalopathy.

Findings:

  • Genetic analysis identified a de novo mutation, p.Leu359Val, in the glial fibrillary acidic protein (GFAP) gene.
  • This specific mutation has not been previously reported in association with Alexander disease.
  • The identified mutation correlated with the observed mild clinical phenotype and imaging findings.

Implications:

  • This case expands the genotypic and phenotypic spectrum of Alexander disease.
  • Understanding genotype-phenotype correlations is crucial for predicting disease progression and prognosis.
  • Further research into GFAP mutations may reveal novel therapeutic targets for leukoencephalopathies.

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