Mitochondrial DNA Depletion Syndrome 1

Background and History: 

This is one of several disorders in which there are multiple changes in the DNA of mitochondria (mitochondria are small bodies in cells responsible for energy production).  These contain small amounts of DNA that require maintenance for proper function which is provided by gene products generated in the nucleus of cells.

Clinical Correlations: 

The gastrointestinal tract is the primary system affected in this condition.  Poor absorption of foodstuffs combined with poor motility, intermittent constipation, vomiting, diarrhea, and bowel inflammation result in weight loss, emaciation, and abdominal pain.  Many patients develop diverticuli (a condition in which small out pouches of the bowel develop) and these often become inflamed and sometimes perforate with severe consequences and even death.  These various symptoms can mimic obstructions of the bowel resulting in unnecessary surgery.

A progressive hearing loss is often present.  Eye movements are restricted and the upper eyelids droop.  Brain imaging often shows loss of brain matter, while nerves outside the brain may be affected as well resulting in weakness in the limbs.  The number of mitochondria is generally reduced and they may contain many changes in their DNA.


This disorder follows an autosomal recessive pattern of inheritance due to a change (mutation) in both members of a specific gene pair.  The clinically normal parents each carry the mutation in one member of the pair and each of their children have a 25% chance of getting both changed genes.

Note that the causative mutation, located in the nuclear DNA, changes the gene product which is needed to maintain DNA in the mitochondria.  Therefore, its clinical impact is the result of mutations in the mitochondrial DNA which is not properly maintained and therefore accumulates mutations that result in disease.

Diagnosis and Prognosis: 

The gastrointestinal complex of symptoms results in considerable discomfort and often a restricted life style that requires frequent medical attention.  Gastroenterologists, nutritionists, and neurologists may be the primary providers for these usually adult patients.  In spite of best efforts lifespan is often shortened.

Additional Information
Autosomal recessive