DGUOK (deoxyguanosine kinase) is a mitochondrial matrix enzyme that catalyzes the phosphorylation of deoxyguanosine and deoxyadenosine, with highest efficiency for deoxyguanosine 1. In non-replicating cells where cytosolic deoxyribonucleotide triphosphate synthesis is downregulated, DGUOK functions as an essential component of the mitochondrial nucleotide salvage pathway, partnering with TK2 to maintain mtDNA synthesis 2. DGUOK deficiency causes mitochondrial DNA depletion syndrome, a group of severe autosomal recessive disorders characterized by impaired mtDNA maintenance and quantitative mtDNA reduction 1. The hepatocerebral phenotype, the most common presentation (74% of DGUOK-deficient patients), manifests as neonatal/infantile-onset cholestatic liver failure with concomitant neurological deterioration including hypotonia, developmental delay, and lactic acidosis 3. Among pediatric patients with indeterminate acute liver failure, DGUOK mutations rank among the three most frequent genetic findings 4. Prognosis is poor, with 1-year survival of 11% for hepatocerebral disease and median disease duration of approximately 5.5 months from symptom onset to death 3. Patients with two truncating variants experience higher mortality and more severe neonatal presentations 3. Liver transplantation remains controversial but may benefit selected patients with minimal neurological involvement 5.