McArdle’s disease

Figure 7. Myophosphorylase deficiency (McArdle s disease) enzyme is absent from muscle fibers but present in smooth muscle cells of blood vessel (arrow).

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

Human creatine kinase -MM MAK33 IgGl Cardiac disease, mitochondrial disorders, inflammatory myopathies, myasthenia, polymyositis, McArdle s disease, NMJ disorders, muscular dystrophy, ALS, hypo and hyperthyroid disorders, central core disease, acid maltase deficiency, myoglobinuria, rhabdomyolysis, motor neuron diseases, A. thaliana A. thaliana 2S2 seed storage protein SP + 0.02-0.4% TSP of fresh leaf extract (10-12% TSP of intercellular fluid) 52... 

Phosphorylase deficiency (McArdle s disease, glycogenosis type V) is an autosomal recessive myopathy caused by a genetic defect of the muscle isoenzyme of glycogen phosphorylase (Fig. 42-1). Intolerance of strenuous exercise is present from childhood, but usually onset is in adolescence, with cramps after exercise [1, 5]. Myoglobinuria occurs in about one-half of patients. If they avoid intense exercise, most patients can live normal lives however, about one-third of them develop some degree of fixed weakness, usually as a late-onset manifestation of the disease. In a few patients, weakness rather than exercise-related cramps and myoglobinuria characterizes the clinical picture. 

The myopathic form of CPT deficiency is due to a defect of CPT II. The gene for CPT II has been localized to chromosome 1, and several mutations have been identified in patients [4]. As in the case of McArdle s disease (see above), one mutation, a serine-to-leucine substitution at codon 113, is far more common than the others in Caucasians and can be screened for in genomic DNA from blood cells, thus potentially avoiding muscle biopsy. 

McArdle s disease is associated with excessive deposits of glycogen in muscle, and Hers disease with its deposition in liver. In both cases phosphorylase levels in the affected tissues are very low. In spite of this, glycogen synthesis is unimpaired, which is incompatible with glyco-genesis occurring through the action of phosphorylase. 

V Muscle glycogen phosphorylase McArdle s disease Exercise-induced cramps rhabdomyolysis renal failure by myoglobinuria... 

Glycogen storage disease type V (McArdle s disease) is caused by a deficiency of myophos-phorylase. It is the most common of the various types of glycogen storage disease, but is still considered rare (about 1 in 100000). 

Phosphofructokinase deficiency (Tarui s disease) is an inborn error of glycogen metabolism characterised by a phosphofructokinase deficiency in the muscles, and associated with abnormal deposition of glycogen in muscle tissues, occasionally with myoglobinuria. The symptoms are similar to those seen in McArdle s disease. Classic Tarui s disease typically presents in childhood with exercise intolerance and anaemia. The fatal infantile variant presents in the first year of life. All reported patients have died by age four years. A late-onset variant manifests itself during later adulthood with progressive limb weakness without myoglobinuria or cramps. It is an autosomal recessive inheritance. Males are slightly more often affected than females. 

BeynonRJ, Bartram C, Hopkins P, Toescu V, Gibson H, Phoenk J, and Edwards RH (1995) McArdle s disease molecular genetics and metabolic consequences of the phenotype. 

The normed muscle concentration of pyridoxal phosphate is of the order of 10 nmol per g in patients with McArdle s disease (glycogen storage disease from congenital lack of glycogen phosphorylase), the muscle content of pyridoxal phosphate is reduced to one-fifth of this. There is some evidence that patients with McArdle s disease show signs of vitamin Be deficiency, su esting that the muscle pool of the vitamin is important in maintenance of vitamin Be homeostasis (Beynon et ed., 1995). 

D-1) Muscle phosphorylase deficiency (Type V GSD McArdle s Disease). Liver phosphorylase is normal, but muscle phosphorylase is deficient. The patient cannot break down muscle glycogen and experiences muscle cramps and weakness with exercise. Muscle biopsy may confirm the enzyme defect. There is no significant rise in lactate in an ischemic exercise test. Magnetic resonance spectroscopy may be useful in diagnosing changes in muscle metabolic function. 

A. Glycogen accumulates because muscle phosphorylase is deficient in McArdle s disease (a glycogen storage disease). 

Type V, also called McArdle s disease, usually presents in the second or third decade with muscle cramps after exercise. Moderate exercise can be sustained, and patients have a second wind, when symptoms disappear if exercise is continued. Increased plasma creatine kinase activities at rest, the failure of ischemic exercise to increase serum lactate concentrations while producing an exaggerated increase in ammonia, myoglobinuria, and diminished activity of muscle phosphorylase establish the diagnosis. Patients respond to oral glucose administration or injections of glucagon. 

Ischemic exercise is usually used for the diagnosis of McArdle s disease and the lack of venous lactate increase is believed to be the sine qua non for the diagnosis. In a patient described by Sahn and Magee5 venous serum lactate increased in the arm after isometric and isotonic ischemic exercise, although the increase was significantly less than in a normal control. Histochemical reactions and biochemical assays confirmed the absence of phosphorylase. Although the symptoms were... 

GSD type V, McArdle s disease Myophosphorylase deficiency, inability to utilize glycogen. See text. 

McArdle s disease causes muscle cramps and muscle fatigue with increased muscle glycogen. Which of the following enzymes is deficient ... 

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