Neonatal Liver Failure: Mitochondrial DNA Depletion Syndrome in the Top of Differential Diagnosis

background: Acute liver failure is a rare and severe condition that can be related to inborn errors of metabolism especially before 1 year of age. Mitochondrial DNA depletion syndrome is on the top of differential diagnosis in neonates. We report the hepatocerebral variant of mitochondrial DNA depletion syndrome in a Syrian family.

A 6 days old baby girl was admitted for lethargy and poor oral intake for 2 days. The baby was born at 41 weeks via C/S for failure to progress. No NICU admission. Family history was significant for a brother dead at 4 months of age due to a liver failure.

On admission the baby was comatous, hypotonic, blood sugar : 1 mmol, hepatomegaly, mildly jaundiced, no bleeding. Neurologic examination showed severe axial hypotonia with intermittent roving eye movements triggered. Investigations showed normal blood gas, normal CK, high lactate, normal ammonia and deranged LFT with severe coagulopathy. Cardiac echography ruled out a congenital heart disease.

Investigations showed normal GALT activity, TMS : non specific increase of ornithine, methionine, tyrosine and arginine. Iron profile normal. Brain and liver MRI normal.

The baby was started on antibiotic, dextrose and multivitaminic cocktail. The liver failure continued to deteriorate and the baby developed a refractory ascitis and died at 2 weeks of life. NGS showed one homozygous mutation on MPV17 gene.

Conclusion: mitochondrial DNA depletion should be considered in the workup of neonatal liver failure.