Treatment of a high cardiovascular risk patient with McArdle's disease with PCSK9 inhibitors. / Tratamiento de un varón con enfermedad de McArdle y muy alto riesgo cardiovascular con inhibidores de PCSK9.

A 60-year-old male with familial combined hyperlipidemia, ischemic heart disease and type 2 diabetes. Since childhood, intolerance to intense exercise. The patient was diagnosed of McArdle's disease after an episode of rhabdomyolysis associated with statins as treatment after a myocardial infarction. Since then, he had been treated with diet, fibrates and ezetimibe with good tolerance, despite this, LDL cholesterol (cLDL) remained >180mg/dl. He started to be treated with alirocumab 150mg/sc every 14 days, with excellent clinical response and a decrease in cLDL to 15mg/dl. Our case shows that PCSK9 inhibitors are effective and safe in patients with muscle diseases who have statin contraindication, and they are a good therapeutic tool for these patients.

[McArdle's disease with insulin resistance caused by obesity].

We reported a 29-year-old woman with McArdle's disease accompanied with insulin resistance. The patient was referred to our hospital because of muscle tenderness, swelling and weakness of lower extremities, and elevated serum CK level. Ischemic forearm exercise test showed no elevation in serum lactate and pyruvate levels. Muscle biopsy revealed significant reduction in phosphorylase activity both histochemically and biochemically. Pre-administration of glucagon had no effect on serum lactate and pyruvate levels after ischemic forearm exercise test while serum glucose elevated. The glucose clamp test confirmed insulin resistance. There was no reduction in number of insulin receptor or activity of tyrosine kinase. Her bodyweight was 78.4 kg and body mass index (BMI) was high as 32.0. Her obesity might be a causative factor of insulin resistance.

The role of lipid peroxidation in McArdle's disease: applications for treatment of other myopathies.

Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress.

Myophosphorylase deficiency: two different molecular etiologies.

Two different forms of myophosphorylase deficiency (McArdle's disease) can be distinguished through the presence or absence of the protein subunit corresponding to phosphorylase in muscle extracts analyzed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Two patients showed a complete absence of the phosphorylase protein subunit, while another patient had an increased quantity of an apparently defective phosphorylase protein subunit. On the basis of these observations, the existence of two distinct subtypes of phosphorylase deficiency can be inferred.