In 2020, Husain et al. [1] reported the various clinical presentations of the 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) variant, from severe cases with acute encephalopathy-like symptoms in the neonatal period, extensive white matter lesions in the cerebral white matter, Leigh encephalopathy-like findings to mild cases of spastic paraplegia in the teenage years with no obvious lesions on brain magnetic resonance imaging (MRI). The gene discussed is HPDL; the disease is Acute encephalopathy.