Early white matter involvement in an infant carrying a novel mutation in ACOX1
Insights
A novel ACOX1 mutation caused a progressive neurological disorder in a child, characterized by early seizures and later white matter degeneration visible on MRI scans.
Area of Science:
- Neuroscience
- Genetics
- Pediatric Neurology
Background:
- Describes a rare pediatric neurological disorder with a distinct two-step clinical progression.
- Highlights the importance of advanced neuroimaging in diagnosing complex neurological conditions.
Observation:
- A child presented with neonatal hypotonia, followed by seizures and later developmental delay and progressive neurological decline.
- Serial head MRI revealed evolving white matter abnormalities, initially in the deep cerebellar nuclei and later extending to cerebellar white matter and brainstem tracts.
Findings:
- Molecular analysis identified a novel mutation in the ACOX1 gene, leading to a truncated protein.
- The observed pattern of white matter involvement suggested an ascending trajectory originating from the deep cerebellar nuclei.
Implications:
- This case expands the known spectrum of ACOX1-related disorders.
- Correlates specific MRI findings with a novel genetic mutation, aiding in future diagnosis and understanding of peroxisomal disorders.
Abstract:
We describe the clinical findings and MRI features observed in a child who presented a two-step disease course: he was hypotonic at birth and soon afterwards developed seizures, which were partially responsive to treatment; he subsequently showed developmental delay and a progressive neurological deterioration with the onset of severe seizures at around three years of age. Head MRI at age 20 days was unremarkable, whereas at 25 months it showed bilateral hyperintensity of the deep cerebellar nuclei; five months later, the signal hyperintensity was also present in the cerebellar white matter and ventral pontine fibre tracts. Molecular analysis revealed a novel ACOX1 mutation, predicting a largely truncated protein. The white matter involvement, which followed an ascending trajectory from cerebellar and brainstem structures to the cerebral hemispheres, seemed to originate from the perinuclear white matter of the deep cerebellar nuclei.
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