Evaluation of protein expression of inflammation and glycogenolysis and its applicability in clinical practice as biomarkers in the evolution of McArdle's disease: correlation with pathogenesis of the clinical, epidemiological and pathological finding

• Grant number: 14/26793-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2015
• End date: March 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alzira Alves de Siqueira Carvalho
• Grantee: Miriam Eva Koch
• Host Institution: Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil

Abstract

McArdle disease, also known as Glycogenosis Type V, was described for the 1st time in1951 by Brian McArdle. It is caused by deficiency of muscle glycogen phosphorylase (myophosphorylase), an enzyme involved in the process of glycogenolysis. It is the most common glycogen storage disease among 13 existing types, occurring in 1:40,000 individuals. The onset occurs in adolescence and is characterized by a great increase of CPK (creatinephosphokinase) at rest, myalgia, muscle cramps and exercise intolerance. Despite the Mendelian pattern of inheritance, autosomal recessive, dominant in males and 50 % of patients have a family history. The diagnosis is made by the clinical picture, elevated CPK at rest, muscle biopsy showing no activity myophosphorylase, ischemic exercise test. The enzyme dosage and molecular analysis confirmed the diagnosis. Recent studies have shown that the pathophysiology of these patients is related to a sequence of events involving muscle myophosphorylase, the mechanism of contraction - relaxation and muscle glycogen synthesis. Therefore, the goal of research is to study these aspects associated with the expression of signaling proteins and their applicability in clinical practice using the dosage of these proteins as biomarkers in disease progression. Will be selected approximately 20 patients with McArdle's disease and 20 healthy subjects as control group. Patients will be subjected to ischemic exercise test modified (TIEM) and Second Wind Fenomenon test conducted at the School of Medicine of ABC. During the TIEM will be collected blood lactate, ammonia, CPK, BUN, creatinine and uric acid. In addition to the biochemical measurements, will hold molecular analysis by studying the expression of glycogen phosphorylase, Glutathione, Thioredoxin reductase, nuclear transcription kappa beta factor, Glycogen synthase kinase 3, and cytochrome C oxidase by PCR in real time. In parallel, we will do genetic study in all patients searching existing mutation using sequencer.