Wellcome Trust Centre For Mitochondrial Research

Mitochondrial DNA depletion syndrome (MDDS)

The term depletion refers to the markedly decreased amount of mitochondrial DNA found in muscle, liver and brain tissues in these disorders. These are severe disorders presenting in early infancy or childhood with profound weakness
encephalopathy, seizures and liver failure. In one form of ‘hepatocerebral’ depletion known as Alpers’ disease or Progressive Neuronal Degeneration of Childhood (PNDC), explosive onset of seizures, developmental delay and spasticity are followed some variable time later by catastrophic liver failure. In the ‘myopathic’ form of depletion profound weakness impairs mobility and eventually involves respiratory muscles leading to severe difficulty in breathing. A number of genes have been associated with specific variations of the depletion syndromes: myopathic (TK2); hepatocerebral (DGOUKPOLG1) and encephalomyopathic (SUCLA2). If a mutation in one of these genes is identified as the cause of disease, it could then be identified during future pregnancies chorionic villous biopsy or amniocentesis