Hospital Sant Joan de Deu, Passeig de Sant Joan de Deu, 2, Esplugues de Llobregat, 08950, Barcelona, Spain.
Department of Pediatrics, Centre for Inborn Errors of Metabolism, Comenius University Children's Hospital, Bratislava, Slovakia.
Orphanet J Rare Dis. 2019 Jan 8;14(1):32. doi: 10.1186/s13023-019-0996-6.
Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales.
This retrospective, observational chart review included patients with NP-C from five expert NP-C centers. Patient disability scores were recorded using three published NP-C disability scales, and a unified disability scale was developed to allow comparison of data from each scale. Disease progression was represented by scores on the unified NP-C disability scale. Patients were stratified as infantile (< 4 years), juvenile (≥ 4 - < 16 years), and adult (≥ 16 years) based on age at diagnosis, and treated ≥1 year and non-treated/treated < 1 year based on the duration of miglustat treatment.
The analysis included 63 patients; the majority (61.9%) were on miglustat therapy for ≥1 year. Ataxia and clumsiness/frequent fall were the most common neurologic symptoms across age groups, whereas, hypotonia and delayed developmental milestones were specific to infantile patients. In both infantile and juvenile patients, visceral signs preceded diagnosis and neurologic signs were noted at or shortly after diagnosis. Adult patients presented with a range of visceral, neurologic, and psychiatric signs in years preceding diagnosis. Patients on miglustat therapy for ≥1 year had a lower mean annual disease progression compared with those untreated/treated < 1 year (1.32 vs 3.54 points/year). A significant reduction in annual disease progression in infantile patients, and a trend towards reduced disease progression in juvenile patients after ≥1 year of miglustat treatment, translated into higher age at last contact or death in these groups.
The type and onset of symptoms varied across age groups and were consistent with descriptions of NP-C within the literature. Miglustat treatment was associated with a reduced rate of disability score worsening in infantile and juvenile patients, both in agreement with increased age at last contact.
尼曼-匹克病 C 型（NP-C）是一种溶酶体脂质贮积病，其特征是进行性神经退行性症状。NP-C 的体征和症状随发病年龄而变化，现有疗法旨在缓解症状和稳定疾病进展。我们报告了疾病进展的特征和相关因素，并使用 NP-C 残疾量表分析了米格列醇治疗对疾病进展和患者生存的影响。
这项回顾性观察性图表回顾包括来自五个 NP-C 专家中心的 NP-C 患者。使用三种已发表的 NP-C 残疾量表记录患者的残疾评分，并开发了一个统一的残疾量表，以允许比较每个量表的数据。疾病进展以统一的 NP-C 残疾量表上的评分来表示。根据诊断时的年龄，将患者分为婴儿期（<4 岁）、青少年期（≥4-<16 岁）和成年期（≥16 岁），并根据米格列醇治疗的持续时间分为治疗≥1 年和未治疗/治疗<1 年。
分析包括 63 名患者；大多数（61.9%）接受米格列醇治疗≥1 年。在所有年龄组中，共济失调和笨拙/经常跌倒都是最常见的神经症状，而婴儿患者则有肌张力低下和发育迟缓。在婴儿和青少年患者中，内脏症状先于诊断，而神经症状则在诊断时或不久后出现。成年患者在诊断前数年出现一系列内脏、神经和精神症状。接受米格列醇治疗≥1 年的患者的平均年疾病进展率低于未治疗/治疗<1 年的患者（1.32 与 3.54 分/年）。婴儿患者接受米格列醇治疗≥1 年后，疾病进展的年增长率显著降低，青少年患者也有减少疾病进展的趋势，这导致这些患者的最后一次就诊或死亡年龄增加。
症状的类型和发病年龄在各年龄组之间存在差异，与文献中 NP-C 的描述一致。米格列醇治疗与婴儿和青少年患者残疾评分恶化率降低相关，这与最后一次就诊时的年龄增加一致。
