Biochemical correlates of neuropsychiatric illness in maple syrup urine disease
Biochemical correlates of neuropsychiatric illness in maple syrup urine disease
复制标题
DOI：
10.1172/jci67217
复制
发表时间：
2013-04-01
影响因子：
15.9
通讯作者：
Strauss, Kevin A.
中科院分区：
文献类型：
--
作者：
Muelly, Emilie R.;Moore, Gregory J.;Strauss, Kevin A.
枫糖尿病（MSUD）是一种支链氨基酸代谢的遗传性疾病，表现为新生儿脑病、间歇性代谢失代偿和慢性氨基酸失衡。饮食管理有助于生存并降低急性危机的风险。肝移植已成为消除急性失代偿风险的有效途径。精神疾病是MSUD的一种并发症，但没有很好地表征，而且仍然知之甚少。我们报告了37例典型MSUD患者（年龄5-35岁，26例接受饮食治疗，11例接受肝移植）的神经精神问题的患病率和特征，并探讨其潜在机制。与26名年龄匹配的对照组相比，MSUD患者在认知、注意力和情绪障碍方面的风险更高。通过定量质子磁共振波谱，我们发现MSUD患者的脑谷氨酸、n -乙酰天冬氨酸（NAA）和肌酸浓度较低，这与特定的神经精神预后相关。无症状新生儿病程和严格的纵向生化控制被证明是优化长期心理健康的基础。移植和未移植MSUD患者的神经精神发病率和神经化学相似。总之，氨基酸失调导致移植后持续存在的神经化学缺陷的异常神经网络，并与神经精神疾病相关。这些发现可能对精神疾病的一般机制提供深入的了解。
Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances. Dietary management enables survival and reduces risk of acute crises. Liver transplantation has emerged as an effective way to eliminate acute decompensation risk. Psychiatric illness is a reported MSUD complication, but has not been well characterized and remains poorly understood. We report the prevalence and characteristics of neuropsychiatric problems among 37 classical MSUD patients (ages 5-35 years, 26 on dietary therapy, 11 after liver transplantation) and explore their underlying mechanisms. Compared with 26 age-matched controls, MSUD patients were at higher risk for disorders of cognition, attention, and mood. Using quantitative proton magnetic resonance spectroscopy, we found lower brain glutamate, N-acetylaspartate (NAA), and creatine concentrations in MSUD patients, which correlated with specific neuropsychiatric outcomes. Asymptomatic neonatal course and stringent longitudinal biochemical control proved fundamental to optimizing long-term mental health. Neuropsychiatric morbidity and neurochemistry were similar among transplanted and nontransplanted MSUD patients. In conclusion, amino acid dysregulation results in aberrant neural networks with neurochemical deficiencies that persist after transplant and correlate with neuropsychiatric morbidities. These findings may provide insight into general mechanisms of psychiatric illness.