Mitochondrial DNA Depletion Syndrome 3

Background and History: 

This is a rare, severe, and fatal congenital liver failure disorder.

Clinical Correlations: 

Infants between birth and 4 months of age have signs of progressive liver failure and most are deceased by one year of age.  They feed poorly and fail to thrive resulting in slow growth.  Muscle tone is poor but reflexes can be exaggerated.  Liver function tests reveal damage to the liver cells and as a result the blood sugar is low and circulating bilirubin is high resulting in jaundice.  Initially the liver and spleen are enlarged but when scarring (fibrosis) follows the liver may shrink in size.

Evidence of brain damage (encephalopathy) with shrinkage of the brain tissue may be present and seizures may occur.  Eye signs include uncoordinated eye movements and nystagmus (dancing eyes).


An autosomal recessive mutation in a gene is responsible for this condition.  The gene change (mutation) has to be present in both members of a specific pair of genes to cause this disorder.  The clinically normal parents who carry one copy, may each contribute it to one in 4 of their offspring generating a risk of 25% that each child will inherit the two gene changes.

Diagnosis and Prognosis: 

The diagnosis can be made at birth or soon thereafter by a collaborating team of pediatricians, neurologists, and gastroenterologists.  There is no treatment for the general condition.  Liver transplantation performed in one infant was unsuccessful and death occurred at less than one year of age as is the case for all who have this condition.

Additional Information
Autosomal recessive