Expanding the Clinical, Pathological, and Molecular Phenotypes of Tetratricopeptide 19 (TTC19) Gene Mutations: A Case...

Tetratricopeptide 19 gene (TTC19) is involved in mitochondrial respiratory chain (MRC) complex III function. Mutations cause developmental delay, Leigh syndrome, and spinocerebellar ataxia. In this report, we highlight the expanding phenotype of TTC19 gene variants. A 28-year-old man with intellectual disability presented with dysarthria, palatal tremors, and cerebellar ataxia of 5 months. After collecting clinical information and blood samples, clinical-exome sequencing was performed. Serum and cerebrospinal fluid lactate levels were elevated. Neuroimaging showed hypertrophic olivary degeneration, and MRC complex III deficiency was found on muscle biopsy. A novel variant of the TTC19 gene was identified, and the patient showed minimal symptomatic improvement with the mitochondrial cocktail. Mitochondrial complex III deficiency has varied ages of onset and multiaxial presentation. This novel variant in TTC19 gene indicated that palatal tremor, hypertrophic olivary degeneration, and axonal neuropathy might be unrecognized manifestations.