The Other Human Genome

In the past 13 years, a new chapter of human genetics, "mitochondrial genetics", has opened up and is becoming increasingly important in differential diagnosis. Although the clinical manifestations of disorders related to mitochondrial DNA (mtDNA) are extremely variable, recent advances in genetic testing aid in the identification of patients. Muscle morphology can give important clues for diagnosis, but histological features alone cannot define a specific disorder. Biochemical analysis may reveal a single enzyme defect, or when multiple activities are affected, suggest an mtDNA mutation. However, definitive diagnosis often requires DNA analysis and documentation of a specific mtDNA abnormality. Disorders associated with mtDNA mutations are associated with a wide variety of syndromes, and owing to the properties and characteristics of mtDNA, these are often transmitted by maternal inheritance. Although therapy for mitochondrial diseases is limited, identification of the molecular defect is important for genetic counseling.