Gold Jessica I, Strong Alanna, Gold Nina B, Yudkoff Marc, Szalda Dava, Jan Sophia, Schwartz Lisa A, Ganetzky Rebecca
Division of Medical Genetics, Department of Pediatrics, Cohen Children's Medical Center, New Hyde Park, New York, USA.
Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA.
J Inherit Metab Dis. 2025 Jan;48(1):e12827. doi: 10.1002/jimd.12827. Epub 2024 Dec 10.
Successful transition to independent adulthood requires intact executive and adaptive function. These neurocognitive domains are frequently impaired in inherited metabolic disorders (IMD), despite optimal management. For many IMDs, the impact of executive and adaptive dysfunction on long-term outcomes remains undefined. Standardized assessments linking neurocognitive status with functional outcomes are needed to improve prognostication and tailor support for affected emerging adults. Maple syrup urine disease (MSUD), a relatively prevalent IMD, is primarily diagnosed in the first week of life through newborn screening. Despite early intervention, executive and adaptive dysfunction persist. We designed a remote, interactive battery of neurocognitive and functional assessments for adults (≥21 years) with MSUD to correlate neurocognition and long-term outcomes. Participants were selectively recruited for racial, ethnic, socio-economic, and geographic diversity. Assessments completed by 28 adults with MSUD (82% diagnosed after symptom onset, 25% from minority communities) show a wide range in educational attainment, employment, and residence. Executive and adaptive function were significantly impaired in adults with MSUD compared to controls. Executive and adaptive deficits correlated negatively with educational attainment, employment, and obtaining skills needed for adult-oriented healthcare or independent living. Clinical history did not predict functional outcomes, but neurocognitive assessments suggest the benefits of pre-symptomatic diagnosis. Independent adulthood is attainable for individuals with MSUD. Routine assessment of neurocognition and interventions targeting executive and adaptive function may improve long-term functional outcomes in IMD.
成功过渡到独立成年期需要完整的执行功能和适应功能。尽管进行了优化管理，但这些神经认知领域在遗传性代谢疾病（IMD）中经常受损。对于许多IMD而言，执行功能和适应功能障碍对长期预后的影响仍不明确。需要将神经认知状态与功能预后联系起来的标准化评估，以改善预后并为受影响的新兴成年人量身定制支持。枫糖尿症（MSUD）是一种相对常见的IMD，主要通过新生儿筛查在出生后第一周内确诊。尽管进行了早期干预，但执行功能和适应功能障碍仍然存在。我们为患有MSUD的成年人（≥21岁）设计了一套远程、交互式的神经认知和功能评估组合，以关联神经认知和长期预后。参与者因种族、民族、社会经济和地理多样性而被有选择地招募。28名患有MSUD的成年人（82%在症状出现后确诊，25%来自少数族裔社区）完成的评估显示，他们在教育程度、就业和居住方面存在很大差异。与对照组相比，患有MSUD的成年人的执行功能和适应功能明显受损。执行功能和适应功能缺陷与教育程度、就业以及获得成人导向医疗保健或独立生活所需技能呈负相关。临床病史无法预测功能预后，但神经认知评估表明症状前诊断有益。患有MSUD的个体可以实现独立成年。对神经认知进行常规评估以及针对执行功能和适应功能的干预措施可能会改善IMD的长期功能预后。
