Welcome to the NORD Physician Guide to Mitochondrial Myopathies. The NORD Online Physician Guides are written for physicians by physicians with expertise on specific rare disorders. This guide was written by Michelangelo Mancuso, MD, PhD, Neurological Clinic, University Hospital of Pisa, Italy and Michio Hirano, MD, Columbia University Medical Center, New York, NY (see acknowledgements for additional information).
NORD is a nonprofit organization representing all patients and families affected by rare diseases. The information NORD provides to medical professionals is intended to facilitate timely diagnosis and treatment for patients.
This guide will focus on primary mitochondrial myopathy (PMM), namely genetic disorders of the mitochondrial respiratory chain affecting predominantly, but not exclusively, skeletal muscle.
Mitochondrial diseases like PMM can be classified genetically into two major groups: those due to mutations in nuclear DNA (nDNA) and others caused by mutations in mitochondrial DNA (mtDNA).
PMM may present at any age, although typically the more severe phenotypes present earlier in life and milder phenotypes present later in life.
The most common phenotype of PMM, observed in about two-thirds of all cases, is progressive external ophthalmoplegia, characterized by bilateral eyelid ptosis associated with a compensatory frontalis muscle contraction and – in severe cases – tilting of the head.
The diagnostic process of PMM may require a complex approach that includes routine and special laboratory tests, exercise physiology study, muscle biopsy for morphology and biochemistry, and molecular genetic screening.
There is currently no available disease-modifying therapy for PMM; therefore, treatment focuses on symptomatic management of disease manifestations and use of a combination of vitamins and supplements (often described as "mito-cocktails").
There are reports on the following related topics in NORD’s online Rare Disease Database for patients, families and the public at: