PDF(Pubmed)
Abstract：
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.
摘要：
芳香族L-氨基酸脱羧酶缺乏症（AADCd）是多巴脱羧酶（DDC）基因中致病性纯合或复合杂合变体引起的一种罕见的隐性代谢紊乱。腺相关病毒载体介导的人DDC基因的基因转移注射到壳核是可用的。典型表现为早发性张力减退，严重的发育迟缓，运动障碍,和自主神经失调.最近,已经报道了轻度甚至非典型的表型，增加诊断挑战。这项多中心研究的目的是确定AADCd在以神经发育障碍（发育迟缓/智力障碍，和/或自闭症）通过干燥血斑（DBS）中的3-O-甲基多巴（3-OMD）检测。及时识别AADCd至关重要，尤其是在非典型表型簇中，因为在轻-中度表型中快速开始治疗时，可以获得更好的结果。在2021年至2023年之间，对390名可能与AADCd相关的非特异性表型患者进行了测试；没有一个结果是阳性。该结果突出表明，要进行AADCd调查的人群应具有更明确的临床特征：与常见体征（张力减退）和/或病理症状（眼病危象和自主神经障碍）有关。有必要继续筛选选定的集群，以通过治疗开始达到诊断并改善长期结果。这强调了新生儿筛查在鉴定AADCd中的作用。
