OMIM ID:
Mitochondrial DNA Depletion Syndrome 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Nystagmus, disconjugate eye movements, and “optic dysplasia” have been noted.
Systemic Features
Infants feed poorly which is frequently associated with vomiting, failure to thrive, and growth delay. They are hypothermic, hypoglycemic, and often jaundiced with signs of liver failure noted between birth and 6 months of age and death by approximately 1 year of age. Hepatosplenomegaly is present early with abnormal liver enzymes, cholestasis, steatosis, and hepatocellular loss followed by cirrhosis with portal hypertension. Metabolic acidosis, hyperbilirubinemia, hypoalbuminemia, and hypoglycemia are often present. Mitochondrial DNA depletion in the liver approaches 84-90%.
All patients have encephalopathic signs with evidence of cerebral atrophy, microcephaly, hypotonia. Hyperreflexia may be present and some infants have seizures. Muscle tissue, however, has normal histology and respiratory chain activity.
Genetics
Inheritance
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.