Aortic Root Dilatation in Taiwanese Patients with Mucopolysaccharidoses and the Long-Term Effects of Enzyme Replacement Therapy

Abstract

Background: Cardiovascular abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular regurgitation and stenosis and cardiac hypertrophy. Only a few studies have focused on aortic root dilatation and the long-term effects of enzyme replacement therapy (ERT) in these patients. Methods: We reviewed echocardiograms of 125 Taiwanese MPS patients (age range, 0.1 to 19.1 years; 11 with MPS I, 49 with MPS II, 25 with MPS III, 29 with MPS IVA, and 11 with MPS VI). The aortic root diameter was measured at the sinus of Valsalva. Results: Aortic root dilatation (z score >2) was observed in 47% of the MPS patients, including 66% of MPS IV, 51% of MPS II, 45% of MPS VI, 28% of MPS III, and 27% of MPS I patients. The mean aortic root diameter z score was 2.14 (n = 125). The patients with MPS IV had the most severe aortic root dilatation with a mean aortic root diameter z score of 3.03, followed by MPS II (2.12), MPS VI (2.06), MPS III (1.68), and MPS I (1.03). The aortic root diameter z score was positively correlated with increasing age (n = 125, p < 0.01). For the patients with MPS II, III, and IV, aortic root diameter z score was also positively correlated with increasing age (p < 0.01). For 16 patients who had received ERT and had follow-up echocardiographic data (range 2.0–16.2 years), the mean aortic root diameter z score change was −0.46 compared to baseline (baseline 2.49 versus follow-up 2.03, p = 0.490). Conclusions: Aortic root dilatation was common in the patients with all types of MPS, with the most severe aortic root dilatation observed in those with MPS IV. The severity of aortic root dilatation worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS appears to stabilize the progression of aortic root dilatation.

Pre-operative Considerations in Adult Mucopolysaccharidosis Patients Planned for Cardiac Intervention

“…Aortopathy is an emerging issue in adult MPS with the exact pathogenesis being unclear ( 77 ), but accumulation of GAGs have been implicated in increased vascular stiffness ( 78 ), aortic narrowing ( 2 ) and aortic root dilatation ( 77 , 79 ). In a cohort of 34 MPS I-VII patients 35.3% developed aortic dilation, with the highest prevalence in MPS IVA (62.5%) ( 79 ) and 66% ( 80 ). A further cohort study of 69 patients demonstrated a prevalence of aortic root dilatation in 39.1% with the highest prevalence in MPS I-H and little effect of ERT on aortopathy ( 81 ).…”

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

“…Through our search, we gathered (at least) 47 patients reported with CVD (MVS, MVR, AVS, ARe), BR, AT, VSD, asymmetric SH and CH and arrhythmogenic RVHCM, which can result in cardiac arrest and recommendation for heart transplant [532,589,[604][605][606][607][608][609] (Table 6, Supplementary Tables S2 and S3). Additionally, we found eight studies with patients displaying cardiac involvement, but the subtype of Sanfilippo syndrome (A, B, C or D) was not specified, and thus they have not been included [512,540,544,556,564,591,600,610].…”

“…Our systematic search identified (at least) 39 MPS-IIIB patients described with cardiac symptoms, including CVD (MVS, MVR, AVS, ARe), to BR, AT, VSD, SH (asymmetric), CH and arrhythmogenic RVHCM, which in some cases resulted in cardiac arrest and/or recommendation for heart transplant [589,[604][605][606]609,[612][613][614] (Table 6, Supplementary Tables S2 and S3). As mentioned in the previous paragraph, we found eight additional studies with MPS_III patients described with cardiac involvement, but the subtype was not specified, thus these studies have been excluded (Supplementary Table S3) [512,540,544,556,564,591,600,610].…”

“…Our search resulted in (at least) 520 MPS-IV patients presenting cardiac symptoms (in some comparative studies in which multiple MPS types were studied together, it was not always possible to determine the exact number of MPS-VI, and thus our count could be slightly underestimated; see Supplementary Table S3). The cardiac symptoms consisted primerily of cardiac valvular disease including VLD, valve thickening, DAR, MVP, AVP, TVP, MVR, ARe, TVR, MI, AI, TI, MVS, TVS and less frequently VSD (intraventricular septal hypertrophy), LHV, HCM and LVCR [497,512,532,540,544,556,564,570,574,579,[589][590][591]596, (Table 6, Supplementary Tables S2 and S3). Cardiac involvement often escalated to congestive HF.…”

The Ehlers–Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism

“…This degree of vascular fragility is not seen in IEM; however, recent studies have brought aortic root dilatation to light as an important complication of MPS and more specifically of MPS IVA (Morquio syndrome) [ 25 ]. Fabry-like stroke events are not present in EDS.…”