Miopatia por deficiência de carnitina-palmitil-transferase: relato de 2 casos com dosagens enzimáticas no tecido muscular

Abstract

We describe two brothers, 25 and 19 years-old, with muscle pain and decreased strength after prolonged exercise; these symptoms are worsened by cold whether of fasting. One of the patients developed recurrent myoglobinuria and had one episode of renal failure. Laboratory investigations were normal between the crises, but during myoglobinuria, serum creatine kinase activity increased 100 times. Electromyography was suggestive of denervation. Muscle biopsy showed increased lipid droplets by the "oil red O" stain and increased activity of succinic dehydrogenase histochemical reaction. Lactate production during ischemia was normal. Biochemical analysis showed decreased carnitine-palmityl-transferase activity in muscle (7.23 and 10.58 nmoles/min/gr; normal range 66.7 +/- 17.3), with normal values for carnitine-octanoyl-transferase and carnitine-acetyl-transferase. The metabolic pathway of fatty acid utilization as an energy source for muscle during exercise in normal and in pathological conditions is discussed.

Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil

“…In 1983, Werneck et al reported the first publication of myopathy due to CPT II deficiency in Brazil, describing two brothers ( Figure 1A ) aged 25 (‘case 1’) and 19 (‘case 2’) years, who presented muscle pain and decreased strength after prolonged exercise, which was made worse by colds. 9 At that time, one of the patients developed recurrent myoglobinuria and episodic renal failure; creatine kinase levels were normal between the crises but increased 100 times during myoglobinuria episodes; needle electromyography suggested denervation; and muscle biopsy showed increased lipid droplets by the ‘oil red O’ stain and increased activity of succinic dehydrogenase histochemical reaction.…”

“…Due to this contribution, one of the authors of the first worldwide publication (Prof Salvatore DiMauro) 2 also shares the authorship of the first Brazilian publication in this field. 9…”

“…The patients reported by Werneck et al had this phenotype. 9 This form presents most frequently in childhood or early adulthood and is usually characterised by attacks of myalgia, weakness, and/or rhabdomyolysis, precipitated mainly by exercise, but also by cold, fever, infection, or prolonged fasting. 1 3 6 8 In severe cases, rhabdomyolysis may lead to myoglobinuria and, consequently, renal failure.…”

“…In this publication, we update the genetic background of the original publication by Werneck et al in 1973. 9 In the original publication, genetic analysis of the CPT2 gene was not available. However, ‘case 2’ is still attending medical appointments in the outpatient clinic of the Neuromuscular Centre at the ‘Hospital de Clínicas da Universidade Federal do Paraná’ (Curitiba, Brazil).…”

“…The article published by Werneck et al also discussed the metabolic pathway of fatty acid utilisation as an energy source for muscle during exercise in normal and pathological conditions with the knowledge of the time ( Figure 1B ). 9 Over the past 40 years since this publication, clinical phenotypes and genetic loci in the CPT2 gene were described, and pathogenic mechanisms have been better elucidated. Three distinct phenotypes of the CPT II deficiency have been reported: a lethal neonatal form (hypoketotic hypoglycaemia and severe hepatomuscular symptoms); a severe infantile hepatocardiomuscular form (hypoketotic hypoglycaemia, liver failure, cardiomyopathy, and myopathy); and the classical myopathic form.…”