The phenotype is neurologically dominant and relatively consistent across reported cases:
Core features:
• Progressive leukoencephalopathy
• Developmental delay followed by psychomotor regression
• Epilepsy
• Cerebellar ataxia
• Spasticity
• Cognitive impairment
Additional reported features:
• Optic atrophy and/or nystagmus
• Peripheral neuropathy
• Hypotonia evolving into spasticity
• Feeding difficulties
Neuroimaging:
• Diffuse, bilateral white matter signal abnormalities, predominantly involving the supratentorial cerebral white matter
• Relative sparing of subcortical U-fibers in early stages, with progression over time
• Cystic degeneration within affected white matter, particularly in periventricular regions
• Gradual progressive cerebral atrophy
• Involvement of the corpus callosum with thinning in later stages
• Cerebellar white matter involvement may be present but is less prominent
Biochemical hallmark:
• Markedly elevated ribitol and D-arabitol in urine, plasma, CSF, and brain (via MR spectroscopy)
Natural history:
• Slowly progressive neurological decline beginning in early childhood
Phenotypic variability exists but understanding of the extent is limited due to the small number of reported cases.
RPIA