Mitochondrial myopathies

What are mitochondrial myopathies (MMs)?

These are a clinically and biochemically heterogeneous group of disorders that have morphologic abnormalities in the number, size, structure, and function of mitochondria. As a group, they are the most common cause of a genetic metabolic myopathy. However, most present with symptoms other than a myopathy (stroke, encephalopathy). The most typical morphologic change on muscle biopsy is the ragged red fiber, a distorted-appearing muscle fiber that contains large peripheral and intermyofibrillar aggregates of abnormal mitochondria. These appear as red deposits on modified Gomori trichrome staining. Many MMs are attributed to defects in one of the 37 genes of the mitochondrial genome, which are maternally inherited. However, nuclear DNA also contains hundreds of genes that produce proteins vital to the mitochondrial structure and function. Diagnosis of mitochondrial disorders occurs via genetic testing of the mitochondrial genome along with those nuclear genes associated with mitochondrial function. Muscle biopsy histology and mitochondrial respiratory chain enzyme activity can prove helpful or confirmatory in some cases.

Syndromes associated with abnormalities of mitochondria have a variety of clinical manifestations, and are thus often called mitochondrial cytopathies. Many present multisystem problems with involvement of the CNS, heart, and skeletal muscle. The skeletal muscle involvement is manifested by progressive proximal muscle weakness, external ophthalmoplegia, and exercise intolerance due to premature fatigue out of proportion to weakness. Mild activity such as walking up one flight of stairs can cause symptoms that resolve with a short rest, but recur with activity. Patients complain of heaviness or burning in the muscles, but most often do not have cramps. Serum CK levels may be normal to moderately elevated. Lactate levels are often elevated at rest or with trivial exercise.

Treatment for MMs often involves treatment with a mitochondrial cocktail, dietary supplementation with creatine monohydrate (0.1 g/kg per day), coenzyme Q10 (5–15 mg/kg per day), and vitamin E (5–15 mg/kg per day). If carnitine levels are low, then treatment with L-carnitine (330 mg, 1–3 capsules up to three times daily) can be tried. Patients with multiple acyl-CoA dehydrogenase deficiency often demonstrate dramatic improvement with riboflavin (100 mg daily). Nearly all patients with MM improve mildly with gradually increased aerobic exercise.

15585

Sign up to receive the trending updates and tons of Health Tips

Join SeekhealthZ and never miss the latest health information

15856