Metabolic myopathies

Metabolic Myopathies Glycogen Storage Disease Disorders of Lipid Metabolism Respiratory Chain Disorders Mitochondrial DNA Abnormalities Myotonias, Periodic Paralyses, and Malignant Hyperpyrexia Myotonias... 

Primary myopathies fall into a number of discrete groups the inherited diseases of muscle, the metabolic myopathies, the neurogenic disorders, and the acquired disorders of muscle. 

The metabolic myopathies are exceptionally complex. Mitochondrial disorders are usually multisystem disorders, in which metabolic dysfunction affects muscle, liver, CNS, and special senses (especially vision) in almost any combination. There is evidence that some forms of mitochondrial disease are inherited, and the preponderance of maternal rather than paternal inheritance is consistent with an abnormality in the mitochondrial genome because almost all (and perhaps all) mitochondria are derived from the ovum. 

To cover these various disorders in an orderly and comprehensive manner, the following sections are devoted, respectively, to the muscular dystrophies the congenital myopathies the metabolic myopathies the myotonias, periodic paralyses, and malignant hyperpyrexia the neurogenic disorders the inflammatory muscle disorders the endocrine myopathies and the drug-induced and toxic myopathies. 

Deficiency of the muscle-specific myoadenylate deaminase (MADA) is a frequent cause of exercise-related myopathy and is thought to be the most common cause of metabolic myopathy. MADA catalyzes the deamination of AMP to IMP in skeletal muscle and is critical in the purine nucleotide cycle. It is estimated that about 1-2% of all muscle biopsies submitted to medical centers for pathologic examination are deficient in AMP deaminase enzyme activity. MADA is 10 times higher in skeletal muscle than in any other tissue. Increase in plasma ammonia (relative to lactate) after ischemic exercise of the forearm may be low in this disorder, which is a useful clinical diagnostic test in patients with exercise-induced myalgia... 

Brumback RA, Feeback DL, Leech RW (1992) Rhabdomyolysis in childhood. A primer on normal muscle function and selected metabolic myopathies characterized by disordered energy production. Pediatr Clin North Am 39 821-858... 

Tirdel et al. [118] researched metabolic myopathy as a cause of the exercise limitation in lung transplant recipients, while Noriyuki et al. [119] evaluated lung tissue oxygenation using NIR spectroscopy. 

G. B. Tirdel, R. Girgis, R. S. Fishman, and J. Theodore, Metabolic Myopathy as a Cause of the Exercise Limitation in Lung Transplant Recipients, J. Heart Lung Transpl., 17(12), 1231-1237 (1998). 

Kreuder J, Borkhardt A, Repp R, Pekrun A, Gottsche B, Gottschalk U, et al. Brief report inherited metabolic myopathy and hemolysis due to a mutation in aldolase A. N Engl J Med 1996 334 1100-4. 

Another strategy is to introduce the gene for the missing enzyme into the patient s cells. This is called gene therapy. This method would also require that the gene for the enzyme be cloned. The DNA would then have to be introduced into the body using a safe procedure that would promote entry into target cells. There are still many obstacles to overcome before this type of treatment will be a reality for sufferers of metabolic myopathy. 

Ronald JA, Tein I. Metabolic myopathies. Seminars in Pediatric Neurology 1996 3 59-98. 

If the phosphorylase pool plays an important part in vitamin B6 kinetics, it might be anticipated that this metabolism would be disturbed in patients suffering from MciVdle s disease, a rare metabolic myopathy caused by an absence of functional muscle glycogen phosphorylase. The absence of this enzyme means that patients cannot break down their muscle glycogen reserves. Other energy sources within the muscle are rapidly depleted... 

Human muscle specimens (M vastus lateralis) without metabolic myopathies were obtained from patients who were undergoing hip surgery. 

Hackett, T.N., Bray, P.F., Zitter, F.A., Nyhan, W.L. and Creer, K.M. (1973), A metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness. /. Pediatr. 83,426. 

Monnens, L., Gabreels, F. and Willems, J. (1975), A metabolic myopathy associated with chronic lactic acidaemia, growth failure and nerve deafness. J. Pediatr., 86,983C. 

---