Hepatocerebral mitochondrial DNA depletion syndrome due to MPV17 mutation presenting with cholestasis and progressive liver failure in an infant

Abstract Mitochondrial DNA depletion syndromes (MDSs) are a group of clinically and genetically heterogeneous disorders. The hepatocerebral form is associated with mutations in the DNA polymerase gamma (POLG), Twinkle helicase (PEO1), and MPV17 genes. This report outlines the clinical, biochemical, and molecular characteristics of an infant diagnosed with hepatocerebral mitochondrial DNA depletion syndrome (MDS), caused by a homozygous mutation in the MPV17 gene. The infant presented at 2 months of age with jaundice, hepatosplenomegaly, hypoglycemia, coagulopathy, and lactic acidosis. Notably, there was a family history of a sibling who had died from a similar illness. The child was managed conservatively and discharged in stable condition. The child remained under medical follow-up and subsequently developed seizures, progressive jaundice, and abdominal distension, ultimately succumbing to liver failure at 10 months of age. The demographic features, physical examination findings, and laboratory investigation results alone are insufficient for the diagnosis, and therefore genetic testing is necessary for patients suspected of having mitochondrial hepatopathies.