Stanford University, School of Medicine, Stanford, CA, USA.
Horizon Therapeutics plc, Lake Forest, IL, USA.
Mol Genet Metab. 2019 Sep-Oct;128(1-2):102-108. doi: 10.1016/j.ymgme.2019.07.009. Epub 2019 Jul 18.
BACKGROUND/AIMS: Urea cycle disorders (UCDs) are rare inborn errors of urea synthesis. US and European consensus statements on the diagnosis and treatment of UCDs were last published in 2001 and 2019, respectively. Recommendations are based primarily on case reports and expert opinion and there is limited agreement or consistency related to long-term management approaches. A clinician survey was conducted to assess current real-world practices and perspectives on challenges and unmet needs.
A 14-item multiple-choice survey was administered to physicians in 2017. Clinicians who reported actively managing at least 1 patient with UCD were eligible to participate. Descriptive statistics were calculated for each survey item (frequencies for categorical variables; means, standard deviations, medians, and ranges for continuous variables).
Sixty-six US clinicians completed the survey (65 geneticists; 1 pediatric neurologist). Over 90% of responders agreed or strongly agreed that even modest elevations in ammonia could cause physiological and functional brain damage; >80% of respondents agreed that asymptomatic UCD patients are at risk of brain damage over time due to mild/subclinical elevations in ammonia. Eighty-six percent of clinicians agreed or strongly agreed with recommending genetic testing for female relatives when a patient is diagnosed with ornithine transcarbamylase deficiency. Ninety-four percent of respondents agreed that patients have better disease control when they are more adherent to their UCD therapy. Nearly 90% indicated that clinicians and patients would benefit from updated UCD management guidance. More than half (53%) of respondents rated the symptoms of UCDs as extremely or very burdensome to the everyday lives of patients and their families; only 8% rated UCD symptoms as slightly or not at all burdensome. The majority of clinicians agreed (48%) or strongly agreed (32%) that caring for a child or family member with a UCD has a negative impact on the quality of life and/or health of family members/guardians (e.g. stress, relationships, ability to work).
This self-reported survey suggests a need for updated and expanded clinical guidance on the long-term treatment and management of UCD patients.
背景/目的：尿素循环障碍（UCDs）是尿素合成的罕见先天性缺陷。美国和欧洲分别于 2001 年和 2019 年发布了关于 UCD 诊断和治疗的共识声明。这些建议主要基于病例报告和专家意见，关于长期管理方法的共识或一致性有限。进行了一项临床医生调查，以评估当前关于挑战和未满足需求的实际做法和观点。
2017 年对医生进行了一项 14 项多项选择调查。有资格参与的临床医生报告积极管理至少 1 名 UCD 患者。对每个调查项目进行描述性统计（分类变量的频率；连续变量的平均值、标准差、中位数和范围）。
66 名美国临床医生完成了调查（65 名遗传学家；1 名儿科神经学家）。超过 90%的受访者同意或强烈同意，即使氨的轻微升高也可能导致生理和功能脑损伤；超过 80%的受访者认为，由于氨的轻度/亚临床升高，无症状 UCD 患者随着时间的推移有脑损伤的风险。86%的临床医生同意或强烈同意，当患者被诊断为鸟氨酸转氨甲酰酶缺乏症时，建议对女性亲属进行基因检测。94%的受访者同意，当患者更遵守 UCD 治疗方案时，患者的疾病控制更好。近 90%的人表示，更新的 UCD 管理指南将使临床医生和患者受益。超过一半（53%）的受访者表示，UCD 症状对患者及其家人的日常生活极其或非常繁重；只有 8%的人认为 UCD 症状略有或根本不繁重。大多数临床医生（48%）或强烈同意（32%），照顾患有 UCD 的儿童或家庭成员会对家庭成员/监护人的生活质量和/或健康产生负面影响（例如压力、关系、工作能力）。
这项自我报告的调查表明，需要更新和扩展关于 UCD 患者长期治疗和管理的临床指南。
