Mucopolysaccharidosis: Cardiologic features and effects of enzyme‐replacement therapy in 24 children with MPS I, II and VI

Abstract

We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme-replacement therapy (ERT) on cardiac disease. Twenty-four children aged 1-18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme-replacement therapy up to 6 years of treatment. At start of therapy, 66% had abnormal cardiac geometric features. Left-ventricular mass index (LVMI) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI. Regurgitation was most severe in a subgroup of young MPS VI patients (<5 years) at the mitral valve. At baseline, all patients had abnormal valves. The ECG showed no clear rhythm or conduction abnormalities; neither, in most patients, did it reflect the hypertrophy. After ERT, the LVMI Z-score normalized in 70% of the patients who had a Z-score > 2. LVMI Z-scores decreased significantly in patients with MPS I and MPS II (p = 0.04 and p = 0.032). Despite ERT, valve regurgitation increased in 60% of the patients. We conclude that all our MPS patients have cardiac abnormalities. The most severe cardiac disease was observed in a subgroup of young MPS VI patients. While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation.

Eficácia e segurança da terapia com idursulfase em pacientes com mucopolissacaridose tipo II, com e sem comparação com placebo: revisão sistemática e metanálise

“…Inicialmente, foram identificados 374 estudos (Figura 1), mas apenas dois eram ECRs, duploscegos, comparando IDS ao placebo 13,14 , enquanto três preencheram critérios como estudos não randomizados 15,16,17 . Nenhum estudo comparando TRE a outro tratamento foi encontrado e não foram obtidas informações adicionais do registro de ensaios clínicos.…”

“…Muenzer et al 13 Muenzer et al 14 Okuyama et al 15 Muenzer et al 16 Brands et al 17 Alterações na amplitude articular do cotovelo (p = 0,0476 -sem demonstração da modificação em graus) na comparação da IDS semanal com placebo 13 . O outro ECR não reporta os resultados desse desfecho, justificando terem ocorrido dificuldades na interpretação, em virtude de heterogeneidade dos pacientes e das aferições 14 .…”

“…As alterações cardíacas foram avaliadas por ecocardiografia em três estudos 14,16,17 . Houve redução significativa da dimensão do septo interventricular durante a diástole em um estudo (-0,36 escore Z/ano, p = 0,05; n = 5) e do índice de massa ventricular esquerda (-0,26 escore Z/ano, p = 0,032; n = 5) 17 , sem modificações significativas na fração de ejeção, morfologia valvar ou outros parâmetros cardíacos, após tratamento com IDS 14,16,17 .…”

Profile of idursulfase for the treatment of Hunter syndrome

“…21 32,33 suggest that ERT has limited effect on the cardiac valves in MPS II patients which are probably only slightly accessible to ERT, whereas it has some effect on cardiac dimension. 31 …”

Biomarker responses correlate with antibody status in mucopolysaccharidosis type I patients on long-term enzyme replacement therapy

“…Almost all patients initially show a significant clinical response to introduction of ERT, with increased forced vital capacity and improvement of endurance as measured by a 6-minute walk test, generally followed by a plateau phase [3,4,8]. Some patients, however, show a significantly less favorable response with only moderate initial improvement or with a gradual loss of treatment efficacy after the plateau phase [3,6,9,10].…”