[P1-203] Expanding clinical spectrum of PNPT1 mutation: from epileptic encephalopathy to Leigh syndrome
The PNPT1 gene, encodes the mitochondrial polynucleotide phosphorylase (PNPase), have been recently reported in a few cases as the cause of severe progressive disease involving multi-organ, including intellectual disability, microcephaly, epilepsy, sensorineural hearing loss, optic atrophy and cardiomyopathy. Here we report two unrelated cases with novel PNPT1 mutations. The first patient was 3-year-old boy and born from non-consanguineous parents after an uneventful pregnancy and showed normal development until 6 months of age. He initially presented with infantile spasms, followed by intractable myoclonic and generalized tonic seizures with developmental arrest. The serial brain magnetic resonance imaging (MRI) revealed progressive brain atrophy and newly appeared T2 signal change in basal ganglia, thalami, midbrain and cerebellum. We found compound heterozygote variants of PNPT1 (A507G/R192X) through whole exome sequencing. The second patient was a 12-year-old girl without any perinatal problems. She showed severe motor developmental delay and poor weight gain since her birth. Also she had severe intellectual disability and seizures. At the time of last evaluation, she was nearly bed-ridden state and showed no social interactions. Brain MRI revealed definite T2 signal change in bilateral basal ganglia at age of 6 years. Novel compound heterozygote mutations of PNPT1 (G382E/L216V) were detected by whole exome sequencing. Our 2 cases could expand the phenotypic spectrum of PNPT1 and highlight the utility of the whole exome sequencing in diagnosis of complex and rare neurologic disorders in children.