Goal attainment in PMM2-CDG: A new approach measuring meaningful clinical outcomes

IF 3.7 2区生物学 Q2 ENDOCRINOLOGY & METABOLISM

Molecular genetics and metabolism Pub Date : 2025-03-19 DOI:10.1016/j.ymgme.2025.109087

Sanne Verberkmoes , Gina L. Mazza , Andrew C. Edmondson , Fernando Scaglia , Seishu Horikoshi , Bryce Kuschel , Mirian C.H. Janssen , Jehan Mousa , Austin Larson , Rameen Shah , Georgia McDonald , Kyriaki Sarafoglou , Gerard Berry , Tamas Kozicz , Christina Lam , Eva Morava

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引用次数: 0

Abstract

Patient-centered outcomes, including patient-reported outcomes (PROs), are increasingly important in healthcare and research, though their use in rare diseases remains limited. In disorders with significant phenotypic variation, selecting appropriate outcome measures is crucial to ensuring the relevance of clinical trials for the patient population.

Phosphomannomutase 2-CDG (PMM2-CDG) involves a complex genotype-phenotype relationship, making it challenging to predict clinical outcomes and select reliable measures for clinical trials. Caused by biallelic pathogenic variants in the PMM2, PMM2-CDG displays highly variable clinical severity, underscoring the need for personalized outcome measures. One such so far unexplored, individualized approach is Goal Attainment Scaling (GAS), which allows patients to set and track personal goals over time.

We evaluated 93 PMM2-CDG patients enrolled in the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) Natural History study, classifying patient goals using the International Classification of Functioning, Disability, and Health (ICF) model, and assessing goal achievement prospectively. We also analyzed potential associations between GAS and factors such as age, sex, genetic background, and disease severity measured by the Nijmegen Progression CDG Rating Scale (NPCRS).

The most common goals set by patients were related to mobility (31.5 %) and communication (26.8 %), with additional goals focused on body function (22.8 %) and independence (18.8 %). Of the 68 patients with follow-up data, 23.5 % showed no improvement in their goals, while 20.6 % improved in all three personal goals. Patients with pathogenic variants affecting the PMM2 dimerization domain had lower GAS improvement scores (M = 1.3 [SD = 1.1]) compared to those without such variants (M = 2.2 [SD = 1.7], p = 0.03). There was no significant correlation between NPCRS score changes and GAS improvement (r = −0.18, p = 0.19).

GAS is a valuable additional outcome measure that ensures clinical improvements are meaningful for patients and their representatives, helping to assess individual goals and overall wellbeing.

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PMM2-CDG的目标实现：衡量有意义的临床结果的新方法

以患者为中心的结果，包括患者报告的结果（PROs），在医疗保健和研究中越来越重要，尽管它们在罕见疾病中的应用仍然有限。在具有显着表型变异的疾病中，选择适当的结果测量对于确保临床试验与患者群体的相关性至关重要。磷酸腺苷转氨酶2-CDG （PMM2-CDG）涉及复杂的基因型-表型关系，这使得预测临床结果和为临床试验选择可靠的测量方法具有挑战性。PMM2- cdg是由PMM2的双等位基因致病变异引起的，其临床严重程度变化很大，因此需要个性化的结果测量。一种迄今尚未开发的个性化方法是目标实现缩放（GAS），它允许患者设定并跟踪个人目标。我们评估了93名参加先天性糖基化疾病联盟（FCDGC）自然史研究前沿的PMM2-CDG患者，使用国际功能、残疾和健康分类（ICF）模型对患者目标进行分类，并对目标实现情况进行前瞻性评估。我们还分析了GAS与年龄、性别、遗传背景和疾病严重程度等因素之间的潜在关联，这些因素由奈梅亨进展CDG评定量表（NPCRS）测量。患者设定的最常见目标与行动能力（31.5%）和沟通能力（26.8%）有关，其他目标主要集中在身体功能（22.8%）和独立性（18.8%）。在68名有随访数据的患者中，23.5%的患者在他们的目标上没有改善，而20.6%的患者在三个个人目标上都有改善。有致病变异影响PMM2二聚体结构域的患者的GAS改善评分（M = 1.3 [SD = 1.1]）低于没有这种变异的患者（M = 2.2 [SD = 1.7], p = 0.03）。NPCRS评分变化与GAS改善无显著相关性（r = - 0.18, p = 0.19）。GAS是一项有价值的额外结果测量，确保临床改善对患者及其代表有意义，有助于评估个人目标和整体健康。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular genetics and metabolism 生物-生化与分子生物学

CiteScore

5.90

自引率

7.90%

发文量

621

审稿时长

34 days

期刊介绍： Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.