Département de neuropédiatrie, GHUEP, Hôpital Armand Trousseau, AP-HP, 75012 Paris, France; Centre de référence neurogénétique, mouvement anormaux de l'enfant, 75012 Paris, France; Sorbonne Université, GRC n° 19, Pathologies Congénitales du Cervelet-LeucoDystrophies and Inserm U 1141, 75012 Paris, France.
Letiam, EA 73 57, Paris South University, 91400 Saclay, France; Service de biochimie, GHUEP Hôpital Armand Trousseau, AP-HP, 75012 Paris, France.
Rev Neurol (Paris). 2018 Nov;174(9):581-588. doi: 10.1016/j.neurol.2018.07.002. Epub 2018 Aug 27.
Neurotransmitter disorders comprise a rapidly expanding phenotypically and genetically heterogeneous group. Most of these disorders start in infancy through to childhood, although some forms may arise in adolescence and adulthood, and have various presentations. They may be overlooked if the phenotype leads to misdiagnoses involving various combinations of developmental disorders, hypotonia and movement disorders (dystonia, hyperkinesia, parkinsonism) or other clinical manifestations, such as sleep alterations and mood disorders. Neurotransmitter metabolite levels in cerebrospinal fluid (CSF) may help us to analyze and better understand the metabolic cascade and changes in dopamine and serotonin synthesis, and also guide genetic testing. Indeed, it is important to recognize these disorders in their early stages as they can be greatly improved by drug treatments, and if clinical responses are insufficient, then other agents that may enhance neurotransmission, such as serotonergic drugs and tetrahydrobiopterin (BH4) supplementation, could be considered. Also, a precise genetic diagnosis should be established by gene panels for dystonia, SNP microarrays and whole-exome sequencing. The present brief survey aims to review the present state of the art for the most commonly described and rare disorders of dopamine and serotonin, as well as cofactor deficiencies and dysfunctions, with an overview of clinical features, diagnostic strategies and treatments. Moreover, although these are mainly disorders of infants and children, many may nevertheless reach adulthood; thus, their evolution and treatments should be well known not only by pediatricians, but by neurologists as well, as the latter may be in charge at the stage of diagnosis (rarely) and during the follow-up of these rare patients.
神经递质紊乱包括一组表型和遗传异质性迅速扩大的疾病。这些疾病大多始于婴儿期到儿童期，尽管有些形式可能在青少年和成年期出现，并具有各种表现。如果表型导致涉及发育障碍、低张力和运动障碍（肌张力障碍、多动、帕金森病）或其他临床表现（如睡眠改变和情绪障碍）的各种组合的误诊，这些疾病可能会被忽视。脑脊液（CSF）中的神经递质代谢物水平可以帮助我们分析和更好地理解代谢级联和多巴胺和 5-羟色胺合成的变化，并指导遗传测试。事实上，重要的是在早期识别这些疾病，因为它们可以通过药物治疗得到很大改善，如果临床反应不足，则可以考虑其他可能增强神经传递的药物，如 5-羟色胺能药物和四氢生物蝶呤（BH4）补充剂。此外，还应通过针对肌张力障碍的基因面板、SNP 微阵列和全外显子组测序来建立精确的基因诊断。本简要综述旨在回顾最常见和罕见的多巴胺和 5-羟色胺以及辅助因子缺乏和功能障碍的疾病的最新研究进展，概述其临床特征、诊断策略和治疗方法。此外，尽管这些疾病主要是婴儿和儿童的疾病，但许多疾病仍然可能会进入成年期；因此，儿科医生和神经科医生都应该了解这些疾病的发展和治疗方法，因为神经科医生可能在诊断阶段（很少见）和这些罕见患者的随访阶段负责。
