Neurological manifestations
Individuals with PI4KA-associated disorders can have a variable clinical phenotype, 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, spastic tetraparesis or spastic paraparesis
Most individuals have a severe neurodevelopmental delay, leading to moderate to severe intellectual disability. There is a normal intelligence in some cases.
• Acquired microcephaly in some patients
• Ataxia
• Seizures (infantile spasms, associated with fever, status epilepticus)
• Dystonia, choreoathetosis
• Nystagmus
• Peripheral neuropathy
Gastrointestinal manifestations
In addition, affected individuals may present with inflammatory bowel disease or multiple intestinal atresia.
Vomiting, diarrhea/constipation or gastroesophageal reflux disease have been reported.
Immunological manifestations
Combined immunodeficiency.
Genitourinary abnormalities
Cryptorchidism, renal cysts and duplication of the collecting system.
PI4KA