Department of Human Neuroscience, Unit of Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Parkinsonism Relat Disord. 2022 Oct;103:105-111. doi: 10.1016/j.parkreldis.2022.08.033. Epub 2022 Sep 7.
l-amino acid decarboxylase deficiency (AADCD) is an ultrarare autosomal recessive defect of biogenic amine synthesis that presents with early-onset encephalopathy progressing to severe neurological impairment and intellectual disability. We aimed to explore neurocognitive and behavioral profiles associated with AADCD and possible factors predicting outcome in more detail.
Nine AADCD patients (23.2 ± 10.3 years; range 8-40) underwent systematic clinical and neuropsychological assessment. Diagnostic levels of CSF 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA), and DDC genotype (as ascertained by American College of Medical Genetics and Genomics grading) were included in the data analysis.
All AADCD patients were affected by intellectual disability and psychiatric disorders. Movement disorders included parkinsonism-dystonia, dysarthria, and oculogyric crises. CSF 5-HIAA and HVA levels at diagnosis had a significant influence on adaptive behavior and executive function performance. Patients homozygous for DDC pathogenetic variants showed lower CSF 5-HIAA and HVA levels and higher Unified Parkinson's Disease Rating Scale scores. The disease showed a self-limiting clinical course with partial improvement under pharmacological treatment (B6 and dopamine mimetic drugs).
Patients with AADCD suffer from neuropsychological and psychopathological impairment, which may be improved but not reversed under the present therapeutic approach. However, cognitive functioning should be specifically examined in order to avoid its underestimation on the basis of movement disorder severity. Genotype and biogenic amine level at diagnosis have an important prognostic value.
L-氨基酸脱羧酶缺乏症（AADCD）是一种极罕见的常染色体隐性缺陷，影响生物胺的合成，表现为早发性脑病，进展为严重的神经功能障碍和智力残疾。我们旨在更详细地探讨与 AADCD 相关的神经认知和行为特征以及可能预测结局的因素。
9 名 AADCD 患者（23.2±10.3 岁；范围 8-40 岁）接受了系统的临床和神经心理学评估。纳入脑脊液 5-羟吲哚乙酸（5-HIAA）和高香草酸（HVA）的诊断水平以及 DDC 基因型（通过美国医学遗传学与基因组学学院分级确定）进行数据分析。
所有 AADCD 患者均存在智力残疾和精神障碍。运动障碍包括帕金森病-肌张力障碍、构音障碍和眼阵挛危象。诊断时的 CSF 5-HIAA 和 HVA 水平对适应行为和执行功能表现有显著影响。DDC 致病性变异纯合子患者的 CSF 5-HIAA 和 HVA 水平较低，统一帕金森病评定量表评分较高。疾病呈自限性临床过程，在药物治疗（B6 和多巴胺模拟药物）下部分改善。
AADCD 患者存在神经心理和精神病理损害，在目前的治疗方法下可能会改善但无法逆转。然而，应特别检查认知功能，以避免基于运动障碍严重程度低估认知功能。基因型和诊断时的生物胺水平具有重要的预后价值。
