P064: TRIT1-associated combined oxidative phosphorylation deficiency-35: Two cases from opposite ends of the epilepsy spectrum

extensive symmetrical abnormalities in the periventricular and deep white matter and thalami.To date, treatment for HMBS-related leukoencephalopathy remains supportive.Here we present the presentation and diagnosis of another individual with adolescent-onset HMBS-related leukoencephalopathy.Case Presentation: A 17-year-old male with mild learning difficulties presented with five months of progressive gait changes and lower extremity paresthesias.He experienced tripping, falling and unsteadiness.Subsequently, he developed painful numbness of his bilateral lower extremities.He became nonambulatory and was unable to attend school in the month prior to presentation.Examination revealed hyperreflexia of the lower extremities, bilateral ankle clonus, widebased gait, and preserved sensation.There were hand tremors and titubation.Diagnostic Workup: Brain magnetic resonance imaging (MRI) revealed bilateral thalamic, subcortical white matter and corpus callosum lesions.Thoracic spine MRI was unremarkable.Ophthalmologic evaluation was only notable for red-green color blindness.Neuroinflammatory work-up was negative.Metabolic screening labs and lysosomal enzyme storage disease panel were unrevealing.Exome and mitochondrial sequencing revealed biparentally inherited variants in HMBS: a paternally inherited pathogenic variant (c.499C>T, p.Arg167Trp) and a maternally inherited variant of uncertain significance (c.674G>A, p.Arg225Gln).Follow-up biochemical testing revealed normal plasma aminolevulinic acid (ALA) and PBG levels, normal urine ALA, elevated urine PBG and decreased erythrocyte PBGD activity.Both parents were found to have mildly decreased PBGD activity.