Neurological manifestations
Individuals with PI4KA-associated disorders can have variable clinical manifestations, ranging from a neurodevelopmental disorder of neonatal onset associated with severe hypomyelinating leukodystrophy and pontocerebellar hypoplasia (or even polymicrogyria in some cases) to spastic paraparesis beginning in adolescence.
Patients may present hypotonia or rigidity of the body.
Most individuals have a severe neurodevelopmental delay, leading to moderate to severe intellectual disability. A normal intelligence is present in some cases.
• Acquired microcephaly in some patients
• Ataxia (loss of muscle coordination)
• Seizures (infantile spasms, associated with fever, prolonged seizures)
• Abnormal movements
• Abnormal ocular movements
• Peripheral neuropathy
Gastrointestinal manifestations
In addition, affected individuals may present with inflammatory bowel disease or multiple intestinal atresia (closure of a natural passage).
Vomiting, diarrhea/constipation or gastroesophageal reflux disease have been reported.
Immunological manifestations
Genitourinary abnormalities