Grier Johnston, Hirano Michio, Karaa Amel, Shepard Emma, Thompson John L P
Mailman School of Public Health (J.G., E.S., J.L.P.T.) and College of Physicians and Surgeons (M.H.), Columbia University Medical Center, New York, NY. J. Grier is now with DOCS GLOBAL, Raleigh, NC; and Massachussetts General Hospital (A.K.), Harvard University, Boston.
Neurol Genet. 2018 Mar 26;4(2):e230. doi: 10.1212/NXG.0000000000000230. eCollection 2018 Apr.
To document the complex "diagnostic odyssey" of patients with mitochondrial disease.
We analyzed data from 210 Rare Diseases Clinical Research Network Contact Registry participants who were patients with a biochemical deficiency or self-reported diagnosis of mitochondrial disease, or their caregivers.
Participants saw an average of 8.19 clinicians (SD 8.0, median 5). The first clinician consulted about symptoms was typically a primary care physician (56.7%), although 35.2% of participants initially sought a specialist. Of note, 55.2% of participants received their diagnosis from a neurologist, 18.2% from a clinical geneticist, and 11.8% from a metabolic disease specialist. A majority of the participants (54.6%) received 1 or more nonmitochondrial diagnoses before their final mitochondrial diagnosis. In their pursuit of a diagnosis, 84.8% of participants received blood tests, 71% a muscle biopsy, 60.5% MRI, and 38.6% urine organic acids. In addition, 39.5% of the participants underwent mitochondrial DNA sequencing, 19% sequencing of nuclear gene(s), and 11.4% whole-exome sequencing.
The diagnostic odyssey of patients with mitochondrial disease is complex and burdensome. It features multiple consultations and tests, and, often, conflicting diagnoses. These reflect disease variety, diagnostic uncertainty, and clinician unfamiliarity. The current survey provides an important benchmark. Its replication at appropriate intervals will assist in tracking changes that may accompany increased popularity of exome testing, more rigorous diagnostic criteria, increased patient reported outcome activity, and trials for promising therapies.
记录线粒体疾病患者复杂的“诊断历程”。
我们分析了210名罕见病临床研究网络联系登记参与者的数据，这些参与者为生化缺陷患者或自我报告诊断为线粒体疾病的患者，或其护理人员。
参与者平均看了8.19位临床医生（标准差8.0，中位数5）。就症状咨询的首位临床医生通常是初级保健医生（56.7%），不过35.2%的参与者最初寻求的是专科医生。值得注意的是，55.2%的参与者由神经科医生做出诊断，18.2%由临床遗传学家做出诊断，11.8%由代谢疾病专科医生做出诊断。大多数参与者（54.6%）在最终的线粒体疾病诊断之前接受过1次或更多次非线粒体疾病诊断。在寻求诊断过程中，84.8%的参与者接受了血液检查，71%接受了肌肉活检，60.5%接受了核磁共振成像检查，38.6%接受了尿有机酸检测。此外，39.5%的参与者进行了线粒体DNA测序，19%进行了核基因测序，11.4%进行了全外显子组测序。
线粒体疾病患者的诊断历程复杂且负担沉重。其特点是多次会诊和检查，且常常存在相互矛盾的诊断。这些反映了疾病的多样性、诊断的不确定性以及临床医生的不熟悉。本次调查提供了一个重要的基准。定期重复进行此项调查将有助于追踪可能伴随外显子组检测普及程度提高、诊断标准更加严格、患者报告结局活动增加以及有前景疗法试验而发生的变化。
