[P1-154] Leigh encephalopathy-like syndrome due to ECHS1 defect in a 1-year-old girl detected by urinary organic acid analysis
Short-chain enoyl-CoA hydratase (SCEH) is a mitochondrial enzyme of the second step of fatty acid oxidation (FAO) cycle. SCEH is encoded by ECSH1 gene, and also involved in the valine metabolism. It was reported recently that 2-methyl-2,3-dihydroxybutyrate (2MDHBA), probably a metabolite derived from valine metabolism, may be a diagnostic marker of ECHS1 defect, which was identified in children with Leigh encephalopathy (LE)-like syndrome. We report here a 1-year-old Japanese girl presenting with LE-like syndrome, showing elevation of 2MDHBA in urinary organic acid analysis. She was born to non-consanguineous parents, and her development had been normal before 10 months of age. At 11 months of age, she presented development regression and nystagmus, following exanthema subitum. At 13 months, poor head control, hypotonia, and involuntary movement as well as nystagmus were noted. Elevation of lactate and pyruvate was seen in serum and CSF. MRI showed symmetrical T2 hyper-intensity in cerebral peduncles and basal ganglia, and magnetic resonance spectroscopy showed strong lactate peak. These strongly suggested LE syndrome. 2MDHBA was elevated in organic acid analysis although GDF15 was within normal range, and compound heterozygous mutations in ECHS1 gene were identified (p.A2V/p.N59S). We concluded that ECHS1 defect could be an important causative disease, and urinary organic acid analysis might be a simple screening method for ECHS1 defect, in LE-like syndrome.