Marian University College of Osteopathic Medicine, Indianapolis, IN, USA.
Section of Developmental and Behavioral Pediatrics, Department of Pediatrics, The University of Chicago, 950 East 61St Street, Suite 207, Chicago, IL, 60637, USA.
BMC Med Genomics. 2023 Apr 11;16(1):78. doi: 10.1186/s12920-023-01510-1.
Tyrosine hydroxylase deficiency (THD) is a rare movement disorder with broad phenotypic expression caused by bi-allelic mutations in the TH gene, which encode for tyrosine hydroxylase (TH) protein. Some patients with THD have improvement in dystonia with carbidopa-levodopa, a synthetic form of dopamine typically used in Parkinson's disease, and are considered to have dopa-responsive THD. THD has been found in 0.5-1 per million persons, although due to overlapping symptoms with other disorders and the need for genetic testing, prevalence is likely underestimated. Existing literature describes some patients with THD having intellectual disability, but comorbid autism spectrum disorder (ASD) has not been reported.
A nearly 3-year-old boy was referred to pediatric neurology due to hypotonia, delayed motor milestones, and expressive speech delay. Whole exome sequencing confirmed tyrosine hydroxylase deficiency, detecting a novel variant p.S307C first reported here. The child was treated with carbidopa-levodopa with an excellent response, resulting in improved balance, fewer falls, and improved ability to jump, run and climb stairs. He was determined to have dopa-responsive THD. Due to his delays in expressive speech, the boy also had an assessment with a developmental and behavioral pediatrician, who identified a pattern of social pragmatic speech delay, sensory sensitivities, and restricted interests, and determined that he met criteria for a diagnosis of ASD.
While ASD can stand alone as a clinical diagnosis, it is also a cardinal feature of other genetically-based neurological disorders. To our knowledge, this is the first case that describes a patient with both disorders. Perhaps THD may be among the genetic disorders linked with ASD.
酪氨酸羟化酶缺乏症（THD）是一种罕见的运动障碍，由 TH 基因的双等位基因突变引起，该基因编码酪氨酸羟化酶（TH）蛋白。一些 THD 患者对卡比多巴-左旋多巴（一种常用于帕金森病的多巴胺合成形式）的肌张力障碍有改善作用，被认为是多巴胺反应性 THD。THD 在每百万人中有 0.5-1 例，尽管由于与其他疾病的症状重叠和需要基因检测，患病率可能被低估。现有文献描述了一些 THD 患者存在智力残疾，但合并自闭症谱系障碍（ASD）尚未报道。
一名近 3 岁男孩因肌张力低下、运动发育迟缓及语言表达延迟，被转至儿科神经科。全外显子组测序证实为酪氨酸羟化酶缺乏症，检测到一种新的变异 p.S307C，这是首次报道。患儿接受卡比多巴-左旋多巴治疗，反应良好，平衡改善，摔倒减少，跳跃、跑步和爬楼梯能力提高。他被诊断为多巴胺反应性 THD。由于他语言表达延迟，男孩还接受了发育和行为儿科医生的评估，该医生发现存在社交语用言语延迟、感觉敏感和兴趣受限的模式，并确定他符合 ASD 的诊断标准。
虽然 ASD 可以作为一个独立的临床诊断，但它也是其他基于遗传的神经发育障碍的主要特征之一。据我们所知，这是首例描述两种疾病共存的病例。也许 THD 可能是与 ASD 相关的遗传疾病之一。
