背景:酸性鞘磷脂酶缺乏症(ASMD)或尼曼-皮克病A型,A/B,B是进步的,限制生命,由鞘磷脂磷酸二酯酶1(SMPD1)基因突变引起的常染色体隐性遗传疾病。有必要增加对儿童对被诊断为ASMD的成年人的发病率和死亡率的理解。
方法:这项观察性回顾性调查分析了来自法国27家医院的ASMD患者的病历,在1990年1月1日至2020年12月31日期间诊断/随访。提取合格的记录以收集人口统计信息,医学/发展史,和死亡率数据。使用Kaplan-Meier生存分析估计从出生到死亡的生存结果;还探讨了标准化死亡率(SMR)。
结果:共有118例ASMD患者的病历(B型[n=94],类型A[n=15],和A型/B型[n=9])进行了评估。大多数患者为男性(63.6%);诊断时的中位[范围]年龄为8.0[1.0-18.0]个月(A型),1.0[0-3]年(A型/B型),和5.5[0-73]年(B型)。总的来说,30名患者在研究完成日期死亡;ASMDA型(n=14)患者的中位[范围]死亡年龄为1[0-3.6]岁,A型/B型(n=6)为8.5[3.0-30.9]年,B型(n=10)为57.6[3.4-74.1]年。A型和A/B型ASMD患者的中位[95%置信区间(CI)]生存年龄为2.0[1.8-2.7]岁和11.4[5.5-18.5]岁,分别。使用SMR[95%CI]分析(3.5[1.6-5.9])探索ASMDB型的生存分析,这表明,在ASMDB型人群中,特定年龄的死亡是法国普通人群的3.5倍。死亡原因多为重度进行性神经变性(A型:16.7%),癌症(B型:16.7%),或未指定(各组:33.3%)。
结论:这项研究表明,ASMD患者的疾病负担很大,死亡率很高,包括成人ASMDB型,在法国。
BACKGROUND: Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease types A, A/B, and B is a progressive, life-limiting, autosomal recessive disorder caused by sphingomyelin phosphodiesterase 1 (SMPD1) gene mutations. There is a need to increase the understanding of morbidity and mortality across children to adults diagnosed with ASMD.
METHODS: This observational retrospective survey analysed medical records of patients with ASMD with retrievable data from 27 hospitals in France, diagnosed/followed up between 1st January 1990 and 31st December 2020. Eligible records were abstracted to collect demographic, medical/developmental history, and mortality data. Survival outcomes were estimated from birth until death using Kaplan-Meier survival analyses; standardised mortality ratio (SMR) was also explored.
RESULTS: A total of 118 medical records of patients with ASMD (type B [n = 94], type A [n = 15], and type A/B [n = 9]) were assessed. The majority of patients were males (63.6%); the median [range] age at diagnosis was 8.0 [1.0-18.0] months (type A), 1.0 [0-3] year (type A/B), and 5.5 [0-73] years (type B). Overall, 30 patients were deceased at the
study completion date; the median [range] age at death for patients with ASMD type A (n = 14) was 1 [0-3.6] year, type A/B (n = 6) was 8.5 [3.0-30.9] years, and type B (n = 10) was 57.6 [3.4-74.1] years. The median [95% confidence interval (CI)] survival age from birth in patients with ASMD type A and type A/B was 2.0 [1.8-2.7] years and 11.4 [5.5-18.5] years, respectively. Survival analysis in ASMD type B was explored using SMR [95% CI] analysis (3.5 [1.6-5.9]), which showed that age-specific deaths in the ASMD type B population were 3.5 times more frequent than those in the general French population. The causes of death were mostly severe progressive neurodegeneration (type A: 16.7%), cancer (type B: 16.7%), or unspecified (across groups: 33.3%).
CONCLUSIONS: This
study illustrated a substantial burden of illness with high mortality rates in patients with ASMD, including adults with ASMD type B, in France.