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Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes.

ABSTRACT: Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by mutations in the GALNS gene, which leads to deficient activity of N-acetylglucosamine-6-sulfate sulfatase. MPS IVA patients usually present skeletal dysplasia, coarse features, short stature, airway obstruction, cervical spinal cord compression, dental abnormalities, and cardiac valvular alterations. Enzyme replacement therapy (ERT) with elosulfase alfa is the only disease-specific treatment available for MPS IVA patients and has been shown to improve important clinical and biochemical parameters; however, little is known about the effects of ERT interruption on these patients. In this article, we report the impact of different periods of treatment interruption on clinical outcomes of 18 MPS IVA patients. All MPS IVA patients included in this case series were treated and followed up in Latin American centers and had been receiving elosulfase alfa intravenously for at least 8 months before ERT was interrupted. Different clinical parameters and assessments were evaluated at variable timepoints following therapy interruption. Altogether, our report indicates that some beneficial ERT effects in MPS IVA patients may last after different periods of treatment interruption, as cardiac and respiratory function improvements. However, worsening of important disease parameters after ERT interruption, such as the increase in uGAGs, pain, joint and skeletal aspects, and surgery indications suggests that treatment discontinuation should be avoided in order to maintain the disease as stable as possible, aiming to optimize these patients' life expectancy and quality of life.

SUBMITTER: Politei J

PROVIDER: S-EPMC7932870 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes.

Politei Juan J Porras-Hurtado Gloria Liliana GL Guelbert Norberto N Fainboim Alejandro A Horovitz Dafne Dain Gandelman DDG Satizábal José María JM

JIMD reports 20210112 1

Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by mutations in the <i>GALNS</i> gene, which leads to deficient activity of N-acetylglucosamine-6-sulfate sulfatase. MPS IVA patients usually present skeletal dysplasia, coarse features, short stature, airway obstruction, cervical spinal cord compression, dental abnormalities, and cardiac valvular alterations. Enzyme replacement therapy (ERT) with elosulfase alfa is the only disease-specific trea ...[more]

PMID: 33728253

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Project description:BackgroundCardiac abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular heart disease and cardiac hypertrophy. However, few studies have focused on the cardiac features of MPS IVA.MethodsWe reviewed the medical records, echocardiograms, and electrocardiograms of 32 Taiwanese patients with MPS IVA (16 males and 16 females; median age, 10.8 years; age range, 1.1 to 29.1 years) as well as the echocardiographic data of six patients who received enzyme replacement therapy (ERT) for 3-6 years.ResultsEchocardiographic examinations (n = 32) revealed 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 of 0.94, 2.70, 0.39, and 3.26, respectively. Z scores > 2 were identified in 25%, 50%, 29%, and 69% of the LVMI, IVSd, LVPWd, and aortic diameter values, respectively. Diastolic dysfunction [reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio < 1)] was identified in four patients (13%), however, the ejection fraction was normal (50-75%) in all of the patients. Sixteen patients (50%) had valvular heart disease and most were of mild degree. Fourteen (44%) had valvular stenosis, and 10 (31%) had regurgitation. The z scores of LVMI, IVSd, LVPWd, and aortic diameter, the severity scores of aortic stenosis and regurgitation, and the existence of a thickened interventricular septum were all positively correlated with increasing age (p < 0.05). For the 14 patients with valve thickening, the z scores of LVMI, IVSd and aortic diameter were all larger than those of the 18 patients without valve thickening (p < 0.05). For two patients who started ERT at a younger age (1.4 and 2.8 years, respectively), the z scores for LVMI, IVSd, and LVPWd all decreased after ERT.ConclusionsA large proportion of the patients with MPS IVA had valvular heart disease and cardiac hypertrophy. Cardiac abnormalities worsened with increasing age in accordance with the progressive nature of this disease. ERT appeared to be effective in stabilizing or reducing cardiac hypertrophy, and better results may have been associated with starting ERT at a younger age.

Dataset Information

Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes.

Publications

Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes.

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