Moreover, a novel splice site mutation in MPV17 gene (c.461 + 1G > C) was identified in a patient with jaundice, muscle weakness, and failure to thrive who died due to hepatic failure at the age of 4 months.
Mutations in human MPV17 have been reported in patients with severe mitochondrial DNA (mtDNA) depletion manifesting as early childhood onset failure to thrive, hypoglycemia, encephalopathy and progressive liver failure.
We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period.
However, when expression of human MPV17 is carried out by adeno-associated virus (AAV)-mediated gene replacement, the Mpv17 knockout mice are able to reconstitute the Mpv17-containing supramolecular complex, restore liver mtDNA copy number and oxidative phosphorylation (OXPHOS) proficiency, and prevent liver failure induced by the KD.
Mutations in the MPV17 gene have been reported in patients who came to medical attention during infancy with liver failure, hypoglycemia, failure-to-thrive and neurological symptoms.
We therefore propose that mutations in the MPV17 gene be considered in the course of evaluating the molecular etiology for isolated, rapidly progressive infantile hepatic failure.