The Neuromuscular Center focuses on the diagnosis and treatment of muscle diseases called metabolic myopathies, which includes inherited disorders of muscle fat, carbohydrate and mitochondrial muscle metabolism. The major energy sources for muscle contraction are glycogen, glucose and fatty acids; glycolytic defects refer to disorders that interfere with the breakdown of glycogen or glucose; lipid disorders refer to defects in the breakdown of long chain fatty acid; and mitrochondrial disorders to defects that impair both carbohydrate and lipid metabolism. Affected patients often complain of lifelong exercise intolerance and fatigue, and frequently are seen by many doctors before a correct diagnosis is made. Such patients may have a defect in one of the metabolic pathways that normally supplies energy to working muscle - the muscle (and the patient) simply "runs out of gas" and may present not only with exercise intolerance, but with pain, weakness and cramps. In its most severe form, muscle breakdown called rhabdomyolysis occurs.
The Biochemistry Lab performs cutting edge functional or exercise testing which allows use of the most sophisticated techniques available to evaluate the metabolic machinery of working muscle. The team of physicians and scientists assembled as the faculty of the Neuromuscular Center have pioneered the application of such techniques to the study of the human muscle disorders. A unique capacity of the Neuromuscular Center is the ability to undertake comprehensive biochemical evaluation of the abnormalities discovered by exercise testing and to diagnose muscle disorders characterized by specific metabolic defects using both invasive (muscle biopsy, blood analysis) and non-invasive (analysis of expired air, determination of the amount of blood pumped by the heart, magnetic resonance spectroscopy) techniques.
Study of these disorders has yielded novel insights into muscle metabolism and illuminated unforeseen relationships between muscle energy metabolism and physiological responses to exercise.
Dr. Ronald Haller is a renowned expert in metabolic disorders of skeletal muscle and has authored more than 100 publications including articles in Science, the New England Journal of Medicine, and the Journal of Clinical Investigation. He has active scientific collaborations with investigators in the United Kingdom, Sweden and Denmark as well as in the United States. His research has centered upon metabolic and physiologic investigation of muscle disorders using exercise testing, magnetic resonance spectroscopy, and detailed biochemical analysis
- The effects of nutritional supplements as therapy for patients with inherited disorders of fat and/or carbohydrate metabolism
- The effects and safety of endurance exercise training as therapy for patients with mitochondrial disorders
- Identifying the potential role of high field 7 Tesla magnetic resonance-imaging (MRI) and -spectroscopy (MRS) for the non-invasive diagnosis of metabolic myopathies
- Ren J, Lakoski S, Haller RG, Sherry AD, Malloy CR. Dynamic Monitoring of Carnitine and Acetylcarnitine in the Trimethylamine Signal after Exercise in Human Skeletal Muscle by 7T 1H MRS. Magn Reson Med. 69:7-17, 2013
- Taivassalo T, Ayyad K, Haller RG. Increased capillaries in mitochondrial myopathy: implications for the regulation of oxygen delivery. Brain 135:53-61, 2012
- Heinicke K, Taivassalo T, Woods H, Wyrick P, Babb T, Haller RG. Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms. Am J Physiol Regul Integr Comp Physiol. 301:R873-R884, 2011
- Vissing J, Duno M, Schwartz M, Haller RG. Deep splice site mutations preserving minimal residual glycogenolysis ameliorate the phenotype in McArdle disease. Brain, 132:1545-1552, 2009
- Mochel F, Knight MA, Tong W-H, Hernandez D, Ayyad K, Taivassalo T, Andersen P, Singleton A, Rouault TA, Fischbeck KH, Haller RG. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genetics, 82:652-60, 2008
- Haller RG, Wyrick P, Taivassalo, T, Vissing J. Aerobic Conditioning: an effective therapy in McArdle Disease. Ann Neurol. 59:922-8, 2006
- Vissing J and Haller RG. The effect of oral sucrose on exercise tolerance in McArdle's disease, N Eng J Med, 349:2503-9, 2003
- Taivassalo T, Dysgaard Jensen T, Kennaway N, DiMauro S, Vissing J, Haller RG. The spectrum of exercise capacity in mitochondrial myopathies: a study of 40 patients. Brain, 126:413-423, 2003
- Haller RG and Vissing J. The spontaneous “second wind” and a glucose-induced second “second wind” in McArdle disease - oxidative mechanisms. Arch Neurol.59:1395-1402, 2002
- Taivassalo T, Abbott A, Wyrick P, Haller RG. Venous pO2 during aerobic forearm exercise: an index of impaired oxidative metabolism in mitochondrial myopathy. Ann Neurol 51:38-44, 2002