Clinical characteristics
The most common clinical presentation of NFU1patients is a severe, early-onset encephalopathy (neonatal period to 1 year of age), which leads to death before the age of 2 years. In neonates, the most frequently reported symptoms include lethargy, muscle weakness, and feeding difficulties; as the disease progresses, neurological regression is commonly observed. Notably, approximately 70% of patients develop pulmonary hypertension. Brain magnetic resonance imaging (MRI) typically reveals leukoencephalopathy or leukodystrophy, often accompanied by early appearing white matter cavitations or cysts.
Patients with later-onset disease and longer survival have also been described, with some surviving into adulthood. This later-onset phenotype is characterized by spastic paraplegia, subacute demyelinating mixed motor–sensory neuropathy, and variable degrees of neurodevelopmental delay. Interestingly, none of these later-presenting individuals have shown evidence of pulmonary hypertension.
NFU1