First cases of MPV17 related mitochondrial DNA depletion syndrome with compound heterozygous mutations in p.R50Q/p.R50W: a case report

Mutations in MPV17 lead to severe mitochondrial DNA depletion syndrome (MTDPS). All known p.R50W variants in MPV17 are lethal. The homozygous variant p.R50Q in MPV17 among patients with Navajo neurohepatopathy is known to allow longer survival, although heterozygous variants p.R50Q have not been reported. This is the first clinical report in compound heterozygosity MPV17 mutation (p.R50W/p.R50Q). Three siblings were admitted due to multiple hepatic nodules; none presented neurological abnormalities. However, they suffered from severe hypoglycemia and cyclic vomiting. The diagnosis of MPV17-related MTDPS was confirmed by detection of a compound heterozygous MPV17 mutation (p.R50W/p.R50Q), and striking reduction of hepatic mitochondrial DNA. One patient developed pediatric-onset of hepatocellular carcinoma. Notably, all patients survived for extended periods, including two patients who received liver transplantation, which contrasted the high mortality rate associated with p.R50W mutations, as previously reported. The p.R50Q mutation might be associated with longer survival and improved liver transplantation outcomes.