Statin‐disclosed acid maltase deficiency

Dear Sir, We read with interest the case of severe, fatal rhabdomyolysis caused by simvastatin treatment [1]. The authors argued against the underestimation of the risk of rhabdomyolysis with the use of statins. We would like to draw attention to another underrated phenomenon related to the use of statins, which is the disclosure of a presymptomatic metabolic myopathy. Clinically important rhabdomyolysis caused by statins is rare, with an overall reported incidence of fatal rhabdomyolysis of 0.15 deaths per 1 million prescriptions per year [2]. In 1–5% of patients, statins produce less serious events such as serum creatine kinase elevations, myalgia, muscle weakness and muscle cramps, all of which may persist after withdrawal [3]. The patient described by Eriksson et al. [1] had a history of cardial infarction and renal insufficiency. Compromised renal function, as observed in this patient, is a well-known risk factor for symptomatic rhabdomyolysis in statin use [3–5]. Additional risk factors are increased serum concentration of statins, hypothyroidism, diabetes and concomitant medications [4, 5]. However, the use of statins has not yet been associated with presymptomatic metabolic myopathy. We therefore report a presymptomatic patient in whom severe myalgia, muscle cramps and increased creatine kinase were triggered by the use of statins. Diagnostic work-up of adult-onset metabolic myopathies was performed, which revealed acid maltase deficiency (acid alpha-1,4 glucosidase) deficiency or adult onset Pompe's disease. A 34-year-old man had suffered from an occipital infarct, after which he recovered completely. He stopped smoking and was prescribed simvastatin for hypercholesterolaemia. Soon afterwards, he reported severe upper abdominal pain. Moreover, he experienced muscle cramps in his calves. His family history was negative for neuromuscular disorders. Physical examination showed liver enlargement and proximal and distal muscle strength was normal. Laboratory investigations revealed increased liver transaminases and creatine kinase. Switch of simvastatin to atorvastatin resulted in neither clinical nor biochemical improvement. Symptoms completely disappeared after withdrawal of statins. The absence of other known risk factors for statin-induced myopathy raised the suspicion of an underlying myopathy. Further investigations into adult-onset metabolic myopathies were performed (Table 1) and acid maltase deficiency was diagnosed. Acid maltase deficiency is inherited as an autosomal recessive trait. The absence of the enzyme acid maltase leads to an excessive accumulation of glycogen in many organs including the central nervous system, heart, liver and skeletal muscles. In muscle, this initially results in exercise-induced myalgia and exercise intolerance. This case shows that presymptomatic acid maltase deficiency can become symptomatic by use of statins. This is analogous to disclosure of diabetes mellitus in previously asymptomatic patients after beginning treatment with corticosteroids. Several factors are involved in statin-induced myopathy, for instance reduced cholesterol content of the membrane, which causes membrane instability [3]. More recent work suggests that altered mitochondrial function is involved in statin-associated myopathy [6]. In summary, muscle cells in acid maltase deficiency are probably more susceptible to exercise-induced injury, whereas statins may impair the ability of the muscle to appropriately respond to, and recover from, this damage. This case report illustrates that acid maltase deficiency can be revealed or disclosed by the use of statins in presymptomatic patients. Symptoms and signs of considerable myopathy during statin use in the absence of risk factors should therefore raise the suspicion of a presymptomatic metabolic myopathy and result in diagnostic work-up of adult-onset metabolic myopathies. There is no conflict of interest of any of the authors.