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. Methods and 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.

From Cryptic Toward Canonical Pre-mRNA Splicing in Pompe Disease: a Pipeline for the Development of Antisense Oligonucleotides

“…In the childhood/adult form of the disease, skeletal muscle cells are the major cells affected without involvement of cardiac or neuronal cells. 47 , 48 This contrasts with classic infantile Pompe disease, in which hypertrophic cardiomyopathy is present at birth, 25 and cognitive decline may progressively develop. 49 , 50 This study identifies AONs for childhood/adult onset Pompe patients.…”

GAA Deficiency in Pompe Disease Is Alleviated by Exon Inclusion in iPSC-Derived Skeletal Muscle Cells

“…In childhood and adult forms of Pompe disease, skeletal muscle wasting is prominent, but cardiac abnormalities are more rare, and there is no evidence for CNS abnormalities 28, 29, 30. A recent report described the generation of myocytes, using MyoD overexpression, from iPSCs derived from adult Pompe patients who did not carry the IVS1 variant 26 .…”

Cardiac troponin T and fast skeletal muscle denervation in ageing

“…Given that fast skeletal muscles are more affected with ageing than slow skeletal muscles across species and cTnT protein is expressed in old skeletal muscle across species found in this study, our finding will provide strong evidence on development of future translational strategies for improving muscle function decline with ageing in human. Because NMJ structure and function deteriorates and cTnT is elevated in the skeletal muscle in various neuromuscular diseases, for instance, Pompe disease 43 and amyotrophic lateral sclerosis, 44 cTnT could also be a potential therapeutic target for such diseases characterized by deteriorations in NMJ structure and function. spectrometry analysis was performed by the Proteomics and Metabolomics Shared Resource supported by the Comprehensive Cancer Center of Wake Forest University grant (P30CA012197; PI: Pasche).…”