Koens Lisette H, de Vries Jeroen J, Vansenne Fleur, de Koning Tom J, Tijssen Marina A J
Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands.
Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands.
Parkinsonism Relat Disord. 2021 Apr;85:124-132. doi: 10.1016/j.parkreldis.2021.02.029. Epub 2021 Mar 2.
We propose a modern approach to assist clinicians to recognize and diagnose inborn errors of metabolism (IEMs) in adolescents and adults that present with a movement disorder. IEMs presenting in adults are still largely unexplored. These disorders receive little attention in neurological training and daily practice, and are considered complicated by many neurologists. Adult-onset presentations of IEMs differ from childhood-onset phenotypes, which may lead to considerable diagnostic delay. The identification of adult-onset phenotypes at the earliest stage of the disease is important, since early treatment may prevent or lessen further brain damage. Our approach is based on a systematic review of all papers that concerned movement disorders due to an IEM in patients of 16 years or older. Detailed clinical phenotyping is the diagnostic cornerstone of the approach. An underlying IEM should be suspected in particular in patients with more than one movement disorder, or in patients with additional neurological, psychiatric, or systemic manifestations. As IEMs are all genetic disorders, we recommend next-generation sequencing (NGS) as the first diagnostic approach to confirm an IEM. Biochemical tests remain the first choice in acute-onset or treatable IEMs that require rapid diagnosis, or to confirm the metabolic diagnosis after NGS results. With the use of careful and systematic clinical phenotyping combined with novel diagnostic approaches such as NGS, the diagnostic yield of late-onset IEMs will increase, in particular in patients with mild or unusual phenotypes.
我们提出一种现代方法，以协助临床医生识别和诊断患有运动障碍的青少年及成人的先天性代谢缺陷（IEMs）。成人期出现的IEMs在很大程度上仍未得到充分研究。这些疾病在神经学培训和日常实践中很少受到关注，并且许多神经科医生认为它们很复杂。IEMs的成人发病表现与儿童期发病的表型不同，这可能导致相当大的诊断延迟。在疾病的最早阶段识别成人发病表型很重要，因为早期治疗可能预防或减轻进一步的脑损伤。我们的方法基于对所有涉及16岁及以上患者因IEM导致的运动障碍的论文进行系统综述。详细的临床表型分析是该方法的诊断基石。特别是对于患有不止一种运动障碍的患者，或伴有其他神经、精神或全身表现的患者，应怀疑存在潜在的IEM。由于IEMs均为遗传性疾病，我们建议将下一代测序（NGS）作为确认IEM的首选诊断方法。生化检测仍然是急性发作或可治疗的IEMs快速诊断的首选，或用于在NGS结果后确认代谢诊断。通过使用仔细且系统的临床表型分析，并结合NGS等新型诊断方法，晚发性IEMs的诊断率将会提高，尤其是对于具有轻度或不典型表型的患者。
