An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia.

Rosa Iodice, Marina Grandis, Chiara Fiorillo, Paola Mandich, Angelo Schenone, Claudio Bruno, Carlo Minetti, Eugenia Rota, Paola Origone, Federico Zara, Livia Pisciotta, Chiara Gemelli, Salvatore Gallone, Serena Patrone, Lucia Ruggiero, Tiziana Mongini, Valeria Prada, Barbara Carlini, Elena Scarsi, Sabrina Fabbri, Lucia Trevisan, Monica Traverso

Journal: Muscle & nerve 2022;65(1):96-104

PMID: 34687219

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Abstract

INTRODUCTION/AIMS

Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition.

METHODS

We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement. All patients underwent a neurological examination and nerve conduction and electromyography studies. The first step of the investigation included a screening for Pompe disease. We then evaluated the patients for myotonic dystrophy type II-related CCTG expansion and excluded patients with copy number variations in the DMD gene. Subsequently, the undiagnosed patients were investigated using a target gene panel that included 20 genes associated with isolated hyperCKemia.

RESULTS

Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings.

DISCUSSION

We have described our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening, and first-line genetic investigations, followed by successive targeted sequencing panels. Both clinical signs and electromyographic abnormalities are associated with increased diagnostic yields.

Address: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genova, Genoa, Italy.; Paediatric Neurology and Muscular Diseases Unit, IRCCS G. Gaslini Institute, Genoa, Italy.; Unit of Medical Genetics, IRCCS G. Gaslini Institute, Genoa, Italy.; Neuromuscular Unit, Department of Neurosciences Rita Levi Montalcini, University of Torino, Torino, Italy.; Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli "Federico II,", Naples, Italy.; Neurogenetic Service, Department of Neurosciences, AOU Città della salute e della scienza, Torino, Italy.; Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genova, Unit of Medical Genetics IRCCS G. Gaslini Institute, Genoa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genova, Unit of Medical Genetics, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.; Neurology Unit, ASL Alessandria, Novi Ligure, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genova, Pediatric Neurology and Muscular Diseases Unit, IRCCS G. Gaslini Institute, Genoa, Italy.; Centre of Experimental and Translational Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences, University of Genova, Unit of Neurology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

DOI: 10.1002/mus.27448

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MeSH Terms: Creatine Kinase, DNA Copy Number Variations, Electromyography, Glycogen Storage Disease Type II, Humans, Muscular Diseases