Heparan sulfate storage in the cardiac conduction system triggers atrioventricular block

Kato, Rie; Miyahara, Hiroaki; Kawano, Tatsuya; Matsuzuka, Atsuko; Noda, Kimiko; Izumi, Tatsuro

doi:10.1016/j.braindev.2016.12.008

Cited by 5 publications

(10 citation statements)

References 8 publications

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“…Second, the first‐degree AV block seen in our patients might be explained by HS storage material in the cardiac conducting system, which was recently reported in a MPS III patient …”

Section: Discussionmentioning

confidence: 53%

“…Second, the first-degree AV block seen in our patients might be explained by HS storage material in the cardiac conducting system, which was recently reported in a MPS III patient. 11 Third, a previous study examining an endomyocardial biopsy in a MPS IIIA patient showed ballooned cardiomyocytes with storage vacuoles containing GAG's. 39 This might be the cause of the early left ventricular dysfunction reported by us.…”

Section: Discussionmentioning

confidence: 94%

“…While CD was previously not considered to be present in MPS III, several recent studies reported cardiac involvement . In addition, CD may also be related to sudden unexpected death reported in some patients …”

Section: Introductionmentioning

confidence: 95%

“…4,[7][8][9] While CD was previously not considered to be present in MPS III, several recent studies reported cardiac involvement. [8][9][10][11][12][13] In addition, CD may also be related to sudden unexpected death reported in some patients. 12 As a number of disease-modifying treatment options for MPS III are currently being investigated, 14 probably leading to an increase in life expectancy with preservation of cognitive function in the near future, extensive knowledge on the prevalence and nature of CD in MPS III is important.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac disease in mucopolysaccharidosis type III

Nijmeijer

Bruin‐Bon

Wijburg

et al. 2019

J of Inher Metab Disea

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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.

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“…Second, the first‐degree AV block seen in our patients might be explained by HS storage material in the cardiac conducting system, which was recently reported in a MPS III patient …”

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cardiac disease in mucopolysaccharidosis type III

Nijmeijer

Bruin‐Bon

Wijburg

et al. 2019

J of Inher Metab Disea

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“…Previous studies have indicated that abnormal catabolism of dermatan sulfate in patients with MPS I, II and VI results in the accumulation of dermatan-sulfated GAGs in cardiac valves, leading to valvular thickening and other cardiac defects [6, 7]. The main storage products of MPS III is heparan sulfate, which has been reported to potentially be an essential constituent of life-long cardiac conduction system plasticity and that its storage results in atrioventricular block [39]. Cardiac lesions may be less prominent in MPS III than in MPS I, II, and VI [37].…”

Section: Discussionmentioning

confidence: 99%

Cardiac characteristics and natural progression in Taiwanese patients with mucopolysaccharidosis III

Lin

Chen

Lin

et al. 2019

Orphanet J Rare Dis

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Background Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of heparan sulfate. Cardiac abnormalities have been observed in patients with all types of MPS except MPS IX, however few studies have focused on cardiac alterations in patients with MPS III. Methods We reviewed medical records, echocardiograms, and electrocardiograms of 26 Taiwanese patients with MPS III (five with IIIA, 20 with IIIB, and one with IIIC; 14 males and 12 females; median age, 7.4 years; age range, 1.8–26.5 years). The relationships between age and each echocardiographic parameter were analyzed. Results Echocardiographic examinations ( n = 26) revealed that 10 patients (38%) had valvular heart disease. Four (15%) and eight (31%) patients had valvular stenosis or regurgitation, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (31%), followed by aortic regurgitation (19%). However, most of the cases of valvular heart disease were mild. Three (12%), five (19%) and five (19%) patients had mitral valve prolapse, a thickened interventricular septum, and asymmetric septal hypertrophy, respectively. The severity of aortic regurgitation and the existence of valvular heart disease, aortic valve abnormalities and valvular stenosis were all positively correlated with increasing age ( p < 0.05). Z scores > 2 were identified in 0, 38, 8, and 27% of left ventricular mass index, interventricular septal end-diastolic dimension, left ventricular posterior wall end-diastolic dimension, and aortic diameter, respectively. Electrocardiograms in 11 patients revealed the presence of sinus arrhythmia ( n = 3), sinus bradycardia ( n = 2), and sinus tachycardia ( n = 1). Six patients with MPS IIIB had follow-up echocardiographic data at 1.9–18.1 years to compare with the baseline data, which showed some patients had increased thickness of the interventricular septum, as well as more patients had valvular abnormalities at follow-up. Conclusions Cardiac involvement in MPS III is less common and milder compared with other types of MPS. The existence of valvular heart disease, aortic valve abnormalities and valvular stenosis in the patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease.

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