Parini Rossella, Deodato Federica, Di Rocco Maja, Lanino Edoardo, Locatelli Franco, Messina Chiara, Rovelli Attilio, Scarpa Maurizio
UOS Malattie Metaboliche Rare, Clinica Pediatrica dell'Università Milano Bicocca, Fondazione MBBM, ASST Monza e Brianza, Monza, Italy.
Division of Metabolic Disease, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Orphanet J Rare Dis. 2017 Jun 15;12(1):112. doi: 10.1186/s13023-017-0662-9.
Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary follow-up with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H.
黏多糖贮积症 I 型 - 胡勒综合征（MPS I - H）是一种代谢性遗传疾病的最严重形式，由编码溶酶体α - L - 艾杜糖醛酸酶的IDUA基因突变引起。MPS I - H是一种罕见的、危及生命的疾病，会发展为多系统疾病，包括进行性神经疾病、上呼吸道阻塞、骨骼畸形和心肌病。异基因造血干细胞移植（HSCT）目前是2至2.5岁之前确诊并接受治疗的MPS I - H患者的治疗金标准，成功率很高。超过这个年龄后，其他因素会影响治疗成功的概率，包括患者的选择、移植物来源和所采用的供体类型。用人重组拉罗尼酶进行酶替代疗法（ERT）也已被证明在改善移植前MPS I - H患者的临床状况以及通过移植期间联合给药改善HSCT结果方面是有效的。然而，即使HSCT成功，长期临床结果仍有很大差异，存在持续的残余疾病负担。因此必须考虑其他策略来改善这些患者的治疗结果：一是通过新生儿筛查进行早期症状前诊断，另一个是确定新的治疗方法。从这个角度来看，尽管新生儿筛查可被视为未来有吸引力的前景，但目前应采取的最佳途径是提高初级保健提供者和儿科医生对该疾病体征和症状的认识，以便患者能及时转诊至合格的参考中心。此外，必须确定敏感的新生化标志物，以更好地界定出生时疾病的临床严重程度，支持随访期间的临床判断，并比较不同疗法的效果。需要对儿童移植后认知发展和残余疾病负担进行长期神经心理学随访。从这个角度来看，参考中心必须保证由专家团队进行多学科随访。只要有可能，参考中心的诊断和干预方案应标准化，以便比较临床数据和评估结果。本综述将聚焦于与MPS I - H管理相关的所有这些关键问题。
