Natural history of echocardiographic abnormalities in mucopolysaccharidosis III

Wilhelm, Carolyn M.; Truxal, Kristen V.; McBride, Kim L.; Kovalchin, John P.; Flanigan, Kevin M.

doi:10.1016/j.ymgme.2018.04.010

Cited by 11 publications

(14 citation statements)

References 18 publications

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“…In all cases the affected valves were the mitral and aortic valve. This is in line with previous studies in MPS III and other MPSs . Both the aortic valve and the mitral valve mainly showed an insufficiency.…”

Section: Discussionsupporting

confidence: 93%

“…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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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 95%

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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“…At an early age, MPS III patients are typically taller with an increased head circumference compared to healthy children, but their growth slows around 5 years of age and by their late teens they are generally shorter than average [41]. Cardiac involvement may be present, consisting typically of mild abnormalities in cardiac valves [32,42].…”

Section: Neurobehavioral Abnormalities and Cognitive Decline As The Mmentioning

confidence: 99%

Molecular Bases of Neurodegeneration and Cognitive Decline, the Major Burden of Sanfilippo Disease

Héon-Roberts

Nguyen

Pshezhetsky

2020

JCM

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The mucopolysaccharidoses (MPS) are a group of diseases caused by the lysosomal accumulation of glycosaminoglycans, due to genetic deficiencies of enzymes involved in their degradation. MPS III or Sanfilippo disease, in particular, is characterized by early-onset severe, progressive neurodegeneration but mild somatic involvement, with patients losing milestones and previously acquired skills as the disease progresses. Despite being the focus of extensive research over the past years, the links between accumulation of the primary molecule, the glycosaminoglycan heparan sulfate, and the neurodegeneration seen in patients have yet to be fully elucidated. This review summarizes the current knowledge on the molecular bases of neurological decline in Sanfilippo disease. It emerges that this deterioration results from the dysregulation of multiple cellular pathways, leading to neuroinflammation, oxidative stress, impaired autophagy and defects in cellular signaling. However, many important questions about the neuropathological mechanisms of the disease remain unanswered, highlighting the need for further research in this area.

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“…Patients with MPS III generally appear unaffected at birth, however clinical manifestations may emerge from 2 to 4 years of age, including intellectual disability, hyperactivity, coarse facial features with broad eyebrows, hirsutism, skeletal dysplasia, degenerative joint disease, hepatosplenomegaly, macrocephaly, and hearing loss [1, 19–21]. Cardiac abnormalities have been observed in patients with all types of MPS, except MPS IX [2–13], however only a few studies have focused on cardiac alterations in patients with MPS III [22–25]. A murine model of MPS IIIB (NAGLU knockout mice, NAGLU −/− ) demonstrated the development of abnormal valve morphology and function in an age-dependent manner associated with increased myocardial vacuolization, inflammation and fibrosis, as well as a dysregulated lysosomal autophagy in the cardiac tissues [26].…”

Section: Introductionmentioning

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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Natural history of echocardiographic abnormalities in mucopolysaccharidosis III

Cited by 11 publications

References 18 publications

Cardiac disease in mucopolysaccharidosis type III

Cardiac disease in mucopolysaccharidosis type III

Molecular Bases of Neurodegeneration and Cognitive Decline, the Major Burden of Sanfilippo Disease

Cardiac characteristics and natural progression in Taiwanese patients with mucopolysaccharidosis III

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