Natural progression of cardiac features and long-term effects of enzyme replacement therapy in Taiwanese patients with mucopolysaccharidosis II

Abstract

Background Cardiac abnormalities have been observed in patients with mucopolysaccharidosis type II (MPS II). The aim of this study was to investigate the cardiac features and natural progression of Taiwanese patients with MPS II, and evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function. Methods The medical records and echocardiograms of 48 Taiwanese patients with MPS II (median age, 6.9 years; age range, 0.1–27.9 years) were reviewed. The relationships between age and each echocardiographic parameter were analyzed. Results The mean z-scores of left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter were 1.10, 2.70, 0.95 and 1.91, respectively. Z scores > 2 were identified in 33%, 54%, 13%, and 46% for LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (MR) (56%), followed by aortic regurgitation (AR) (33%). The severity of mitral stenosis (MS), MR, aortic stenosis (AS), AR, and the existence of valvular heart disease were all positively correlated with increasing age (p < 0.01). We also compared the echocardiographic parameters between two groups: (1) 12 patients who had up to 17 years of follow-up echocardiographic data without ERT, and (2) nine patients who had up to 12 years of follow-up data with ERT. The results showed that z-score changes of LVMI significantly improved in the patients who received ERT compared to those who did not receive ERT (0.05 versus 1.52, p < 0.05). However, the severity score changes of MS, MR, AS, and AR all showed gradual progression in both groups (p > 0.05). Conclusions High prevalence rates of valvular heart disease and cardiac hypertrophy were observed in the MPS II patients in this study. The existence and severity of cardiac hypertrophy and valvular heart disease in these patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS II appeared to be effective in stabilizing or reducing the progression of cardiac hypertrophy, but it only had a limited effect on valvulopathy.

Phenotypic and genetic characteristics of 130 patients with mucopolysaccharidosis type II: A single-center retrospective study in China

“…In our study, valve abnormalities were the most commonly observed cardiac manifestation of MPS II. The most common specific manifestations observed were mitral/tricuspid valve regurgitation (71.9%), aortic/pulmonary valve regurgitation (36.8%), in agreement with the report by Lin et al (2021). Therefore, echocardiography should be checked regularly (Scarpa et al, 2011).…”

Drosophila D-idua Reduction Mimics Mucopolysaccharidosis Type I Disease-Related Phenotypes

“…Muscle-specific downregulation of D-idua led to death at pupal stage suggesting that D-idua is a key player in muscle development and/or maintenance. This possibly reminds of musculoskeletal difficulties, as well as the important cardiac involvement, typical of MPS I patients [ 57 , 58 , 59 ]. Our analysis further suggested a role of D-idua in CNS development and functionality.…”

Early Neonatal Cardiac Phenotype in Hurler Syndrome: Case Report and Literature Review

“…The natural history of MPS has shown that cardiac abnormalities in these individuals worsen with age. It has been demonstrated that initiating ERT in these patients can help to stabilize and even reverse cardiomyopathy [ 24 , 25 , 26 ]. As a result, early discovery and initiation of treatment are crucial for improved outcomes, which can be accomplished by neonatal screening.…”