REVIEW ARTICLE Aminotransferases and muscular diseases: A disregarded lesson. Case reports and review of the literature Claudio Veropalumbo, 1 Ennio Del Giudice, 2 Gabriella Esposito, 3 Sergio Maddaluno, 1 Lucia Ruggiero 4 and Pietro Vajro 1 Pediatric 1 Liver and 2 Neurology Units of the Department of Pediatrics, 3 Department of Biochemistry and Medical Biotechnology, Biotecnologie Avanzate, CEINGE and 4 Department of Neurological Sciences, University of Naples ‘Federico II’, Napoli, Italy Abstract: The aim of this study was to call the attention to the often disregarded message that hypertransaminasemia may be a marker of both liver and muscle diseases by presenting personal case reports and a systematic literature review. Three male children (mean age 5.7 years) were inappropriately addressed, during the last 12 months, to our paediatric liver unit for diagnostic work-up of a chronic hypertransaminasemia of unknown origin. In one of them, a liver biopsy had already been performed. On admission, physical examination, evaluation of serum levels of creatine kinase, and dystrophin genetic testing finally led to a diagnosis of muscular dystrophy. One hundred fourteen similar cases, 21 with unnecessary liver biopsy, were found by Medline search. Expensive and invasive tests planned to investigate liver diseases should be postponed until alternative sources of increased serum aminotransferases, primarily myopathic injury, have been excluded. Key words: children; creatine kinase; hypertransaminasemia; muscular dystrophy. Although the need of considering hypertransaminasemia as a possible marker of muscle disease has been appropriately under- lined by several world-wide reports, 1–18 still this concept seems not deeply rooted in everyday clinical practice. 19 We therefore describe our experience with three children affected by Duchenne/Becker muscular dystrophy (DBMD), referred to our paediatric liver unit because of unexplained hypertransami- nasemia, during the last 12 months. A Medline search on similar cases, performed by using the terms ‘Duchenne Becker’ and/or ‘muscular dystrophy’ and/or ‘myopathy’, is presented as well. Case Reports We report on three male Italian patients, mean age 5.7 years, referred to our paediatric hepatology unit for prolonged (6–24 months, mean 15 months) hypertransaminasemia in the absence of other liver function test abnormalities (Table 1). This finding was incidental in all three cases. Before admission, all patients had already undergone several physical examinations and laboratory tests. One of them (no. 3) had also been hospitalised. Hypertransaminasemia had been diagnosed as cryptogenic because laboratory tests aimed at investigating the most common liver diseases were negative or within normal limits, namely, viral infections (hepatitis B and C, Epstein–Barr virus and cytomegalovirus serum markers), as well as autoimmune (nuclear, smooth muscle and liver–kidney microsomes serum antibodies; serum immunoglobulins), genetic-metabolic (alpha a1 antitrypsyn, ceruloplasmin serum levels and sweat test) and nutritional (anti-tissue transglutami- nase, anti-gliadin immunoglobulin G and immunoglobulin A serum antibodies, and body mass index and waist circumference plus ultrasonographic bright liver evaluation) disorders. In patient no. 3, a liver biopsy only showed mild steatosis. On admission to our unit, an accurate familiar and personal clinical history and an in-depth physical examination were obtained in all patients. Tests carried out in order to define the degree and the origin of hypertransaminasemia included stan- dard liver function tests (serum bilirubin, aminotransferases, gammaglutamyltranspeptidase, albumin and immunoglobulins, and prothrombin time). A further diagnostic work-up in order to re-evaluate the most common causes of liver disease, as well as muscular enzymes, and creatine kinase (CK) fractions was also performed. The genetic tests used to identify Key Points 1 Recognition of increased serum aminotransferases as a marker of muscular involvement still remains neglected in clini- cal practice. 2 When examining a child with elevated serum aminotrans- ferases, it is mandatory to search for positive Gower’s sign and to look at her/his legs for possible calf pseudohypertrophy. 3 Testing specific markers of muscle disease such as creatine kinase and aldolase should be performed at the beginning of the diagnostic algorithm for apparently healthy patients with hypertransaminasemia. Correspondence: Prof Pietro Vajro, Department of Pediatrics, University of Naples ‘Federico II’, Via S. Pansini 5, 80131 Napoli, Italy. Fax: +081 746 2375; email: vajro@unina.it Accepted for publication 6 December 2009. doi:10.1111/j.1440-1754.2010.01730.x Journal of Paediatrics and Child Health (2010) © 2010 The Authors Journal compilation © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians) 1