The clinical features of this disease include:
- Global developmental delay
- Developmental regression
Central Nervous System:
- Reduction in the brain volume (especially of the white matter)
- Intractable seizures
- Microcephaly
- Delayed speech and language development
- Motor delay
- Movement abnormalities
- Ventriculomegaly
- Absent myelination
- Hypoplastic corpus callosum
- Cerebellar hypoplasia
- Cystic encephalomalacia
- Hypoplastic optic nerves
- Hypoplasia of the optic discs
- Abnormal tracking and focusing
- Irregular eye movements
- Cortical blindness
- EEG abnormalities (e.g. slowing of the background activity, hypsarrhythmia, diffuse delta-subdelta activity, spike waves)
- Peripheral hypertonia
- Cerebral palsy
- Gastroesophageal reflux
Other abnormalities (reported in Dr. Janette Mailo’s patient):
- Global cerebral atrophy
- Hypomyelination
- Axial hypotonia
- Swallowing difficulties
- Early thelarche
- Female hirsutism
- Increased pipecolic acid
A severe phenotype of the disease usually results in early death.