Nardecchia Francesca, Ricciardi Giacomina, Carducci Claudia, Mastrangelo Mario, Manti Filippo, Pisani Francesco, Leuzzi Vincenzo
Department of Human Neuroscience, Child Neurology and Psychiatry Unit, Sapienza University of Rome, Rome, Italy.
Department of Experimental Medicine - Sapienza University of Rome, Rome, Italy.
Parkinsonism Relat Disord. 2025 Jul;136:107886. doi: 10.1016/j.parkreldis.2025.107886. Epub 2025 May 23.
Aromatic amino acid decarboxylase defect (AADCd) is an ultrarare autosomal recessive condition due to pathogenetic DDC variants, presenting with early psychomotor delay, movement disorders, and autonomic dysregulation, leading to severe neurological and intellectual disability. Intracranial AAV2-mediated DDC delivery proved to improve the natural history of the disease. We explored the usefulness of the assessment in CSF of metabolic biomarkers of the disease [3-O-methyldopa (3-OMD), 5-hydroxyindolacetic acid (5-HIAA), and homovanillic acid (HVA)], for the post-treatment clinical monitoring.
We collected clinical and CSF neurotransmitter data from 30 published patients and a personal case, to assess the relationship between post-treatment clinical and metabolic variations in subjects with concomitant clinical and CSF evaluation before and at least 6 months after the surgery.
HVA levels increase in many, but not all, patients with a broad variability. No correlation was found between clinical improvement and biogenic amine repletion in CSF. No correlation was detected between pre-treatment clinical severity score and post-treatment HVA variation. Low 5-HIAA and high 3-OMD were not affected by the therapy.
Current evidence suggests CSF metabolites do not overcome the predictive value of clinical observation on clinical outcomes and should be reserved for patients unresponsive to the therapy.
芳香族氨基酸脱羧酶缺陷症（AADCd）是一种极为罕见的常染色体隐性疾病，由致病的DDC基因变异引起，表现为早期精神运动发育迟缓、运动障碍和自主神经调节异常，导致严重的神经和智力残疾。颅内腺相关病毒2型介导的DDC递送已被证明可改善该疾病的自然病程。我们探讨了评估脑脊液中该疾病代谢生物标志物[3 - O - 甲基多巴（3 - OMD）、5 - 羟吲哚乙酸（5 - HIAA）和高香草酸（HVA）]对于治疗后临床监测的有用性。
我们收集了30例已发表患者及1例个人病例的临床和脑脊液神经递质数据，以评估在手术前及术后至少6个月同时进行临床和脑脊液评估的患者中，治疗后临床变化与代谢变化之间的关系。
许多（但并非所有）患者的HVA水平升高，且变化范围广泛。脑脊液中生物胺补充与临床改善之间未发现相关性。治疗前临床严重程度评分与治疗后HVA变化之间未检测到相关性。低5 - HIAA和高3 - OMD不受治疗影响。
目前的证据表明，脑脊液代谢物并不能超越临床观察对临床结局的预测价值，应仅用于对治疗无反应的患者。
