Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States of America.
Stratevi, LLC, Boston, MA, United States of America.
Mol Genet Metab. 2021 Sep-Oct;134(1-2):182-187. doi: 10.1016/j.ymgme.2021.06.011. Epub 2021 Jul 1.
Niemann-Pick Disease Type C (NPC) is an ultra-rare progressive neurodegenerative disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes that lead to premature death, with most individuals dying between 10 and 25 years of age. NPC can present at any age and many individuals with NPC may be misdiagnosed or undiagnosed. A key challenge with recognizing NPC is the heterogeneous and nonspecific clinical presentation. Currently, there are no approved treatments for NPC in the United States; miglustat, an FDA-approved treatment for Gaucher disease, is used off-label for NPC and GM1 gangliosidosis.
To estimate the number of people in the United States that 1) have an NPC diagnosis 2) have an NPC diagnosis and/or are treated off-label with miglustat for NPC and 3) are likely to have NPC.
For the first two objectives, patients were identified using the Symphony Integrated DataVerse database (Oct 2015-Jan 2020). To identify the number of people with NPC for Objective 1, cases of NPC were defined as any patients with an ICD-10 code of E75.242 (NPC) during the study period. Objective 2 expands upon Objective 1, including (a) patients from Objective 1 and (b) patients with documented miglustat use (NDC 43975-0310 or 10,148-0201) who did not have any claim with Gaucher disease (ICD-10 E75.22) or GM1 gangliosidosis (ICD-10 E75.1) during the study period. For the third objective, published NPC incidence (1 per 89,000 live births) and expected mortality estimates were applied to the 2018 United States birth rate (11.6 per 1000) and population size (326.7 million).
A total of 308 million unique individuals were represented in the database. Of these, 294 individuals had an NPC diagnosis, yielding an identified NPC prevalence of 0.95 per million people in the United States. 305 individuals were diagnosed with NPC and/or were treated with miglustat without having a diagnosis for either Gaucher or GM1 gangliosidosis, yielding an NPC diagnosed or treated prevalence of 0.99 per million people in the United States. Based on the published literature, there are an estimated 42 new NPC cases per year. Applying this number to the distribution of NPC type (based on age of neurologic symptom onset) and corresponding mortality estimates generates an estimated 943 prevalent cases of NPC, or 2.9 cases of NPC per million people in the United States.
NPC is an ultra-rare, progressive neurodegenerative disease with approximately 1 per million people in the United States diagnosed with or treated off-label for NPC. Given that NPC is often misdiagnosed or undiagnosed, the estimated prevalence from the epidemiology calculations (2.9 per million) approximates the number of NPC cases if disease awareness, screening and diagnosis efforts were enhanced.
尼曼-皮克病 C 型（NPC）是一种由 NPC1 或 NPC2 基因的常染色体隐性突变引起的超罕见进行性神经退行性疾病，导致患者早亡，大多数患者在 10 至 25 岁之间死亡。NPC 可在任何年龄发病，许多 NPC 患者可能被误诊或漏诊。识别 NPC 的一个关键挑战是其表现具有异质性和非特异性。目前，美国尚无 NPC 的批准治疗方法；米格列醇是一种 FDA 批准用于治疗戈谢病的药物，被用于 NPC 和 GM1 神经节苷脂贮积症的标签外治疗。
估计美国有 1）NPC 诊断 2）NPC 诊断和/或 NPC 用米格列醇标签外治疗 3）可能患有 NPC 的人数。
对于前两个目标，使用 Symphony Integrated DataVerse 数据库（2015 年 10 月至 2020 年 1 月）确定患者。为了确定目标 1 中的 NPC 人数，将 NPC 病例定义为研究期间任何具有 NPC 国际疾病分类第 10 版（ICD-10）代码 E75.242（NPC）的患者。目标 2 扩展了目标 1，包括（a）目标 1 中的患者和（b）有记录的米格列醇使用（NDC 43975-0310 或 10,148-0201）的患者，他们在研究期间没有任何戈谢病（ICD-10 E75.22）或 GM1 神经节苷脂贮积症（ICD-10 E75.1）的索赔。对于第三个目标，应用 NPC 的已发表发病率（每 89000 例活产 1 例）和预期死亡率估计值，乘以 2018 年美国出生率（每 1000 人 11.6 例）和人口规模（3.267 亿）。
数据库中共有 3 亿人。其中，294 人被诊断为 NPC，美国 NPC 的患病率为每百万人中有 0.95 人。305 人被诊断为 NPC 或未经戈谢病或 GM1 神经节苷脂贮积症诊断而接受米格列醇治疗，美国 NPC 诊断或治疗的患病率为每百万人中有 0.99 人。根据已发表的文献，每年估计有 42 例新的 NPC 病例。将这一数字应用于 NPC 类型（基于神经症状发病年龄）的分布和相应的死亡率估计值，可产生估计的 943 例 NPC 现患病例，或美国每百万人中有 2.9 例 NPC。
NPC 是一种超罕见的进行性神经退行性疾病，在美国约有每百万人中有 1 人被诊断为 NPC 或 NPC 用米格列醇标签外治疗。鉴于 NPC 经常被误诊或漏诊，如果提高疾病意识、筛查和诊断工作，根据流行病学计算得出的估计患病率（每百万人 2.9 例）接近 NPC 病例数。
