Child Neurology and Psychiatry Unit, Department of Pediatrics, Presidio Ospedaliero Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
Pediatrics and Neonatology Unit, Maternal and Child Health Department, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy.
Genes (Basel). 2023 Sep 21;14(9):1828. doi: 10.3390/genes14091828.
Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd.
芳香族 L-氨基酸脱羧酶缺乏症（AADCd）是一种罕见的常染色体隐性遗传代谢疾病，由多巴脱羧酶（DDC）基因的致病性纯合或复合杂合变异引起。腺相关病毒载体介导的人 DDC 基因转移已可用于治疗。典型表现为早发性肌张力低下、严重发育迟缓、运动障碍和自主神经功能障碍。最近，报道了一些轻度甚至非典型表型，增加了诊断的挑战。本多中心研究的目的是通过检测干血斑（DBS）中 3-O-甲基多巴（3-OMD）来确定以神经发育障碍（发育迟缓/智力障碍和/或自闭症）为特征的表型聚类患者中 AADCd 的患病率。快速识别 AADCd 非常重要，尤其是在非典型表型聚类中，因为在轻度至中度表型中快速开始治疗会获得更好的结果。在 2021 年至 2023 年期间，对 390 名可能与 AADCd 相关的非特异性表型患者进行了检测，均未得到阳性结果。这一结果表明，应在具有更明确临床特征的人群中进行 AADCd 调查：与常见体征（肌张力低下）和/或特征性症状（眼震危象和自主神经功能障碍）相关。有必要继续对选定的聚类进行筛查，以通过开始治疗来诊断并改善长期预后。这突显了新生儿筛查在识别 AADCd 中的作用。
