Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou, 310009, China.
Metab Brain Dis. 2021 Dec;36(8):2273-2281. doi: 10.1007/s11011-021-00799-0. Epub 2021 Aug 4.
Aceruloplasminemia (ACP) is a rare disorder of iron overload resulting from ceruloplasmin (CP) variants. Because of its rarity and heterogeneity, the diagnosis of ACP is often missed or misdiagnosed. Here, we aim to present a clinical spectrum of ACP and raise more attention to the early diagnosis. Whole exome sequencing (WES) was performed in a Chinese female patient suspected with ACP and her clinical data were collected in detail. The PubMed databases was searched for published ACP patients within the last decade, and we present a systematic review of their clinical features with data extracted from these researches. A novel pathogenic variant (c.2689delC) and a known pathogenic variant (c.606dupA) within ceruloplasmin gene were identified in our patient and confirmed the diagnosis of ACP. Then we reviewed 51 ACP patients including the case we reported here. A possible timeline of symptoms was discovered, anemia appears first (29.7 years old on average), followed by diabetes (37.3 years old) and finally neurological symptoms (50.7 years old). The delay in diagnosis was significantly shortened in patients without neurological symptoms. Biochemical triad including anemia, low to undetectable serum ceruloplasmin, low serum iron and/or hyperferritinemia, showed better sensitivity in diagnosis than clinical triad including diabetes, neurological symptoms, and retinal degeneration. Due to the variable symptom spectrum, patients with ACP often visit different departments, which can lead to misdiagnosis. Clinical attention needs to be paid to symptoms and tests that have a warning effect. Prompt diagnosis in the early stage of the disease can be beneficial.
亚铁氧化酶蛋白血症（ACP）是一种罕见的铁过载疾病，由亚铁氧化酶蛋白（CP）变异引起。由于其罕见性和异质性，ACP 的诊断常常被忽视或误诊。在这里，我们旨在展示 ACP 的临床谱，并引起对早期诊断的更多关注。对一名疑似患有 ACP 的中国女性患者进行了全外显子组测序（WES），并详细收集了她的临床数据。在过去十年中，我们在 PubMed 数据库中搜索了已发表的 ACP 患者，并对从这些研究中提取的数据进行了系统评价，以展示他们的临床特征。在我们的患者中发现了亚铁氧化酶蛋白基因中的一个新的致病性变异（c.2689delC）和一个已知的致病性变异（c.606dupA），从而确诊了 ACP。然后，我们回顾了 51 名 ACP 患者，包括我们报告的病例。发现了一个可能的症状时间表，贫血首先出现（平均年龄 29.7 岁），其次是糖尿病（37.3 岁），最后是神经症状（50.7 岁）。没有神经症状的患者的诊断延迟明显缩短。包括贫血、血清亚铁氧化酶蛋白水平低至无法检测、血清铁和/或铁蛋白水平升高在内的生化三联征在诊断中的敏感性优于包括糖尿病、神经症状和视网膜变性在内的临床三联征。由于症状谱的多变性，ACP 患者经常就诊于不同科室，这可能导致误诊。临床需要注意具有警示作用的症状和检查。早期诊断疾病可以带来益处。
