Grant Nathan, Sohn Young Bae, Ellinwood N Matthew, Okenfuss Ericka, Mendelsohn Bryce A, Lynch Leslie E, Braunlin Elizabeth A, Harmatz Paul R, Eisengart Julie B
Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of Korea.
Mol Genet Metab Rep. 2022 Feb 2;30:100845. doi: 10.1016/j.ymgmr.2022.100845. eCollection 2022 Mar.
Hunter syndrome, or mucopolysaccharidosis (MPS) II, is a rare lysosomal disorder characterized by progressive, multi-system disease. As most symptoms cannot be reversed once established, early detection and treatment prior to the onset of clinical symptoms are critical. However, it is difficult to identify affected individuals early in disease, and therefore the long-term outcomes of initiating treatment during this optimal time period are incompletely described. We report long-term clinical outcomes of treatment when initiated prior to obvious clinical signs by comparing the courses of two siblings with neuronopathic Hunter syndrome (c.1504 T > G[p.W502G]), one who was diagnosed due to clinical disease (Sibling-O, age 3.7 years) and the other who was diagnosed before disease was evident (Sibling-Y, age 12 months), due to his older sibling's findings. The brothers began enzyme replacement therapy within a month of diagnosis. Around the age of 5 years, Sibling-O had a cognitive measurement score in the impaired range of <55 (average range 85-115), whereas Sibling-Y at this age received a score of 91. Sibling-O has never achieved toilet training and needs direct assistance with toileting, dressing, and washing, while Sibling-Y is fully toilet-trained and requires less assistance with daily activities. Both siblings have demonstrated sensory-seeking behaviors, hyperactivity, impulsivity, and sleep difficulties; however, Sibling-O demonstrates physical behaviors that his brother does not, namely biting, pushing, and frequent elopement. Since the time of diagnosis, Sibling-O has had significant joint contractures and a steady deterioration in mobility leading to the need for an adaptive stroller at age 11, while Sibling-Y at age 10.5 could hike more than 6 miles without assistance. After nearly a decade of therapy, there were more severe and life-limiting disease manifestations for Sibling-O; data from caregiver interview indicated substantial differences in Quality of Life for the child and the family, dependent on timing of ERT. The findings from this sibling pair provide evidence of superior somatic and neurocognitive outcomes associated with presymptomatic treatment of Hunter syndrome, aligned with current considerations for newborn screening.
亨特综合征，即黏多糖贮积症（MPS）II型，是一种罕见的溶酶体疾病，其特征为进行性多系统疾病。由于大多数症状一旦出现便无法逆转，因此在临床症状出现之前进行早期检测和治疗至关重要。然而，在疾病早期很难识别出受影响的个体，因此对于在此最佳时间段开始治疗的长期结果描述并不完整。我们通过比较两名患有神经病变型亨特综合征（c.1504 T>G[p.W502G]）的同胞兄弟的病程，报告了在明显临床体征出现之前开始治疗的长期临床结果。其中一名因临床疾病被诊断（同胞O，3.7岁），另一名因哥哥的检查结果在疾病明显之前被诊断（同胞Y，12个月）。兄弟俩在确诊后一个月内开始接受酶替代疗法。在5岁左右时，同胞O的认知测量得分处于受损范围<55（平均范围85 - 115），而同胞Y在这个年龄的得分为91分。同胞O从未完成如厕训练，在如厕、穿衣和洗漱方面需要直接帮助，而同胞Y已完全学会如厕，在日常活动中需要的帮助较少。两兄弟都表现出寻求感官刺激的行为、多动、冲动和睡眠困难；然而，同胞O表现出他哥哥没有的身体行为，即咬人、推搡和频繁走失。自确诊以来，同胞O出现了明显的关节挛缩，活动能力持续恶化，导致在11岁时需要使用适应性婴儿车，而同胞Y在10.5岁时无需帮助就能徒步超过6英里。经过近十年的治疗，同胞O出现了更严重且危及生命的疾病表现；来自照顾者访谈的数据表明，儿童和家庭的生活质量存在显著差异，这取决于酶替代疗法的治疗时机。这对同胞兄弟的研究结果为亨特综合征症状前治疗带来更好的躯体和神经认知结果提供了证据，这与目前新生儿筛查的考虑因素一致。
