Centro de Genetica Medica, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira/FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Mol Genet Metab. 2013 May;109(1):62-9. doi: 10.1016/j.ymgme.2013.02.014. Epub 2013 Mar 5.
Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.
Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated.
A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved.
The prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population.
黏多糖贮积症 VI 型(MPS VI)是一种进行性、慢性和多系统溶酶体贮积病,具有广泛的疾病谱。已有研究报道,接受 rhASB(重组人芳基硫酸酯酶 B;galasulfase,Naglazyme®,BioMarin Pharmaceutical Inc.)酶替代疗法(ERT)的 MPS VI 患者在临床和生化方面有改善,因此,早期诊断和干预对于获得最佳患者结局至关重要。但很少有研究纳入五岁以下的儿童。本报告描述了 34 名五岁以下开始接受 galasulfase 治疗的 MPS VI 患者。
从患者病历中收集五岁以下开始治疗的患者数据。评估导致诊断的常见症状的基线和随访评估,以及用于评估疾病进展和治疗效果的症状。
ERT 治疗与尿 GAG 水平呈显著负相关。在有基线和随访生长数据的患者中,47%的患者保持在治疗前的生长曲线上,或在治疗后移至更高的百分位数。在有基线和随访睡眠研究的 9 名患者中,5 名患者未受影响,1 名最初有轻度睡眠呼吸暂停的患者有改善。还报告了心脏、眼科、中枢神经系统、听力、手术干预和发育的数据。没有患者因不良反应而停止治疗,所有治疗后出现的不良反应均得到解决。
每周 1mg/kg IV 给予 galasulfase ERT 的规定剂量被证明是安全有效的,可以减缓和/或改善疾病的某些方面,尽管应密切监测与疾病自然史相关的并发症,尤其是心脏瓣膜受累和脊髓压迫。对这组儿童进行长期随访调查将提供有关早期治疗以及在这一年轻患者群体中疾病进展和治疗效果和安全性的进一步信息。