Predominant Corticospinal Tract Involvement in a Late Infant with Krabbe Disease

Area of Science:

• Neuroscience
• Genetics
• Pediatric Neurology

Background:

• Krabbe disease is a rare lysosomal storage disorder affecting the nervous system.
• Late-infantile Krabbe disease typically presents with severe neurological deficits.
• Corticospinal tract involvement on MRI is more commonly associated with adult-onset forms of Krabbe disease.

Observation:

• A case of late-infantile Krabbe disease presented with developmental regression and spastic quadriplegia.
• Brain MRI revealed predominant corticospinal tract involvement, an atypical finding for this age group.
• Biochemical assays showed very low galactocerebrosidase activity in lymphocytes and skin fibroblasts.

Findings:

• Genetic testing identified compound heterozygous mutations in the galactocerebrosidase (GALC) gene: c.635_646 delinsCTC and c.1901T>C [p.L618S].
• The c.1901T>C [p.L618S] mutation is known to be associated with late-onset Krabbe disease phenotypes.
• This specific combination of mutations is hypothesized to underlie the unusual MRI findings in this late-infantile case.

Implications:

• The findings suggest that certain GALC mutations may lead to atypical presentations of Krabbe disease, including specific MRI patterns.
• There may be undiagnosed or late-diagnosed cases of Krabbe disease, particularly in populations with a higher prevalence of these mutations (e.g., Japanese patients).
• Pediatricians should maintain a high index of suspicion for Krabbe disease in infants with developmental regression and spasticity, even with atypical MRI findings.