Cardiac disease in mucopolysaccharidosis type III

Abstract

Mucopolysaccharidosis type III (MPS III; Sanfilippo disease) is primarily characterized by neurocognitive decline with limited somatic disease. Only few reports addressed cardiac disease (CD) in MPS III. We investigated the prevalence of CD in a relatively large cohort of patients. In this cross‐sectional study, extensive echocardiographic studies were performed in 30 MPS III patients (16 patients <18 years), all without clinical symptoms of CD. Results were compared to data from matched controls. The mean global longitudinal strain on speckle‐tracking echocardiography (STE) was impaired in both pediatric and adult patients vs controls (resp. −18.4% vs −20.7%; mean difference 2.25, 95% CI 0.61‐3.89, P = 0.009 and −16.9% vs −19.5%; mean difference 2.64, 95% CI 0.78‐4.49, P = 0.007), indicating early systolic dysfunction. Left ventricle ejection fraction (LVEF) was normal in pediatric patients and (slightly) impaired in adult patients vs controls (48.7% vs 55.8%, P = 0.002). Tissue Doppler imaging (TDI) showed significantly slower early diastolic velocities (e′) compared to controls indicative for diastolic dysfunction. Furthermore, mitral and aortic valve abnormalities were prevalent (43% and 33% of patients, respectively). Finally, 15.6% of the patients had a first‐degree atrioventricular block on electrocardiography (ECG). The impaired STE reveals early, subclinical LV dysfunction which is supported by results of TDI. In addition, mild valvular disease and ECG abnormalities are prevalent. The lowered LVEF in adult patients suggests that the LV dysfunction is progressive, and may ultimately lead to clinical myocardial disease when patients live longer due to an effective disease‐modifying treatment of which a number of options are now in clinical trials.

Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses

“…MPS was related to myocardial deformation and more impaired diastolic function and a decline in the global LV systolic mechanics, despite globally preserved LV ejection and shortening fractions. These results were consistent with those of previous studies [21,27,28].…”

“…Consequently, using myocardial deformation imaging in clinical practice may be of value in the early diagnosis of myocardial dysfunction. However, STE has not yet been broadly used to evaluate myocardial mechanics in patients with MPS [21,27,28]. In this study, we aimed to determine the cardiac structure and function of Taiwanese patients with various MPS types using 2D STE and conventional echocardiography.…”

Cardiac characteristics and natural progression in Taiwanese patients with mucopolysaccharidosis III

“…Although LV systolic function according to ejection fraction and shortening fraction values was normal in all of our patients, however, ejection fraction and shortening fraction values are parameters that show abnormalities when there is substantial LV dysfunction. Speckle-tracking echocardiography is a marker for early, subclinical LV dysfunction which was recently reported in patients with MPS III by Nijmeijer et al [23]. In our study, a reversed E/A ratio (< 1) was identified in one patient (4%).…”

“…Cardiac involvement in MPS III has been reported to be less common and milder compared with the other types of MPS [2, 10, 20–23, 37]. Nijmeijer et al [23] reported mitral valve abnormalities and aortic valve abnormalities in 13/30 (43%) and 10/30 (33%) patients with MPS III, respectively. Consistently, echocardiographic examinations in our cohort also revealed that 35 and 27% of the patients had mitral valve abnormalities or aortic valve abnormalities, respectively.…”

“…In relation to grade 1 MR, Kampmann et al [40] described that it was a common finding in the pediatric population in their experience, thus they did not consider MR grade 1 in their study results of valve abnormalities in MPS II. However, in the few original studies focusing on cardiac alterations in patients with MPS III by Wilhelm et al [22] and Nijmeijer et al [23], they both reported the findings of grade 1 MR in their results. Our report was consistent with the latter studies.…”