title: Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease.
abstract: BACKGROUND
  Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury.
  
  
  RESULTS
  In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values <14 ng/L). Cardiac troponin I levels were normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (P<0.001). None of the abnormal ECGs recorded in 21 patients were indicative of acute myocardial infarction, and there were no differences in cTnT levels between patients with and without (n=90) abnormalities on ECG (median 28 ng/L in both groups). The median left ventricular mass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue.
  
  
  CONCLUSIONS
  Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions.
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Stephan C A
authors.initials: SC
authors.lastname: Wens
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Gerben J
authors.initials: GJ
authors.lastname: Schaaf
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Michelle
authors.initials: M
authors.lastname: Michels
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Kruijshaar
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Tom J M
authors.initials: TJ
authors.lastname: van Gestel
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Stijn
authors.initials: S
authors.lastname: In 't Groen
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Joon
authors.initials: J
authors.lastname: Pijnenburg
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Dick H W
authors.initials: DH
authors.lastname: Dekkers
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Jeroen A A
authors.initials: JA
authors.lastname: Demmers
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Lex B
authors.initials: LB
authors.lastname: Verdijk
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Esther
authors.initials: E
authors.lastname: Brusse
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.).
authors.forename: Ans T
authors.initials: AT
authors.lastname: van der Ploeg
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.). w.pijnappel@erasmusmc.nl p.a.vandoorn@erasmusmc.nl.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: van Doorn
authors.affiliation: From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (G.J.S., T.J.M.v.G., S.G., J.P., A.T.v.d.P., W.W.M.P.P.); Proteomics Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); Netherlands Proteomics Center, Rotterdam, The Netherlands (D.H.W.D., J.A.A.D.); and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands (L.B.V.). w.pijnappel@erasmusmc.nl p.a.vandoorn@erasmusmc.nl.
authors.forename: W W M Pim
authors.initials: WW
authors.lastname: Pijnappel
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D005260:Female; D005786:Gene Expression Regulation; D006009:Glycogen Storage Disease Type II / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019210:Troponin I / Q000097:blood; D020107:Troponin T / Q000097:blood*
chemical_list: D019210:Troponin I; D020107:Troponin T; D003402:Creatine Kinase
keywords: creatine kinase; echocardiography; mass spectrometry; myocardial infarction; troponin T