Liver transplantation in a boy with TFAM mutation associated mtDNA depletion syndrome

Mitochondrial transcription factor A (TFAM) deficiency may cause mtDNA depletion syndrome, which manifests as neonatal liver failure or primary ovarian insufficiency, hearing loss, seizures, and intellectual disability. Treatment focusing on symptomatic management, and the clinical prognosis remains poor. Here, we describe a novel case of TFAM mutation presenting with progressive neonatal cholestasis, hypoglycemia and abnormal amino acid profiling. The patient progressed to liver failure at 6 months of age but did not exhibit neurological involvement. No morphologic abnormalities were observed in muscle biopsy, while mtDNA copy number was reduced in comparison to age- and tissue-matched controls. After liver transplantation, liver biochemistries and blood amino acid profiling normalized three weeks later. Moreover, the boy was doing well post-transplant without any clinical concerns, and his development and neurological examination remain normal 33 months after liver transplantation. Our report suggests that liver transplantation appears to have a favorable profile in such patients.