Limited diagnostic value of enzyme analysis in patients with mitochondrial tRNA mutations

• Published in: Muscle & nerve Vol. 41; no. 5; pp. 607 - 613
• Main Authors: Wibrand, Flemming, Jeppesen, Tina D., Frederiksen, Anja L., Olsen, David B., Duno, Morten, Schwartz, Marianne, Vissing, John
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2010; Wiley
• Subjects: 3243A>G; Adolescent; Adult; Aged; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; Diseases of striated muscles. Neuromuscular diseases; Enzymes - analysis; Enzymes - metabolism; Errors of metabolism; Female; Genetic Testing; Humans; Lactic Acid - analysis; Lactic Acid - blood; large-scale deletions; Male; Medical sciences; Metabolic diseases; Middle Aged; Mitochondrial Myopathies - diagnosis; Mitochondrial Myopathies - enzymology; Mitochondrial Myopathies - genetics; mitochondrial myopathy; Muscle Fibers, Skeletal - enzymology; Muscle Fibers, Skeletal - pathology; Muscle, Skeletal - enzymology; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Neurology; Oxygen Consumption - physiology; Point Mutation - genetics; Predictive Value of Tests; respiratory chain enzyme analysis; RNA - genetics; RNA, Transfer - genetics; single; single, large‐scale deletions; tRNA gene mutations; Young Adult; Human; Nervous system diseases; Neuromuscular diseases; Oxygen; tRNA gene mutations; Myotonia; Metabolic diseases; 3243A>G; Muscular fiber; Enzymopathy; Congenital disease; Genetic disease; single; Striated muscle disease; Mitochondria; Myotonic dystrophy; Biopsy; large-scale deletions; respiratory chain enzyme analysis; Deletion; Muscle; Mitochondrial myopathy; Mutation; Histochemistry
• ISSN: 0148-639X; 1097-4598; 1097-4598
• DOI: 10.1002/mus.21541

We evaluated the diagnostic value of respiratory chain (RC) enzyme analysis of muscle in adult patients with mitochondrial myopathy (MM). RC enzyme activity was measured in muscle biopsies from 39 patients who carry either the 3243A>G mutation, other tRNA point mutations, or single, large‐scale deletions of mtDNA. Findings were compared with those obtained from asymptomatic relatives with the 3243A>G mutation, myotonic dystrophy patients, and healthy subjects. Plasma lactate concentration, maximal oxygen uptake, and ragged‐red fibers/cytochrome c–negative fibers in muscle were also determined. Only 10% of patients with the 3243A>G point mutation had decreased enzyme activity of one or more RC complexes, whereas this was the case for 83% of patients with other point mutations and 62% of patients with deletions. Abnormal muscle histochemistry was found in 65%, 100%, and 85% of patients, respectively, in these three groups. The results indicate that RC enzyme analysis in muscle is not a sensitive test for MM in adults. In these patients, abnormal muscle histochemistry appears to be a better predictor ofMM. Muscle Nerve, 2010