AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.
AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.
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DOI：
10.1002/jimd.12247
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发表时间：
2020-09
影响因子：
4.2
通讯作者：
Flint L
中科院分区：
文献类型：
--
作者：
Pearson TS;Gilbert L;Opladen T;Garcia-Cazorla A;Mastrangelo M;Leuzzi V;Tay SKH;Sykut-Cegielska J;Pons R;Mercimek-Andrews S;Kato M;Lücke T;Oppebøen M;Kurian MA;Steel D;Manti F;Meeks KD;Jeltsch K;Flint L
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神经发育障碍，其特征是多巴胺、去甲肾上腺素、肾上腺素和5-羟色胺合成受损，导致运动、行为和自主神经症状的复杂综合征。这项回顾性研究通过医生和/或护理人员对详细的标准化问卷的回答，评估了一个大型AADCD患者国际队列的症状和发育结局。来自23个国家的63例患者（60%为女性;年龄6个月至36岁，中位年龄7岁; 58例存活）参与了研究。发病时的常见症状（中位年龄3个月，范围0 - 12个月）为张力减退、发育迟缓和/或眼球转动危象。97%的2 - 12岁患者存在眼球转动危象，所有年龄组的大多数患者都发生了眼球转动危象，并且在儿童早期往往最严重。突出的非运动症状是睡眠障碍、情绪烦躁和进食困难。大多数受试者（70%）有严重的运动障碍，表现为头部控制缺失和最小的自主运动，而17%的受试者有轻度运动障碍，能够独立行走。多巴胺激动剂是最有可能产生一些症状获益的药物，但与剂量限制性副作用（运动障碍、失眠、易怒、呕吐）相关，导致25%的时间停药。我们队列的年龄分布（70%的受试者年龄<13岁）以及观察到与老年患者相比，年轻患者中具有更严重疾病表型的患者比例更高，均表明重度疾病患者在儿童期存在显著的死亡风险。
Aromatic l‐amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty‐three patients (60% female; ages 6 months‐36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0‐12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises were present in 97% of patients aged 2 to 12 years, occurred in the majority of patients in all age groups, and tended to be most severe during early childhood. Prominent non‐motor symptoms were sleep disturbance, irritable mood, and feeding difficulties. The majority of subjects (70%) had profound motor impairment characterized by absent head control and minimal voluntary movement, while 17% had mild motor impairment and were able to walk independently. Dopamine agonists were the medications most likely to produce some symptomatic benefit, but were associated with dose‐limiting side effects (dyskinesia, insomnia, irritability, vomiting) that led to discontinuation 25% of the time. The age distribution of our cohort (70% of subjects under age 13 years) and the observation of a greater proportion of patients with a more severe disease phenotype in the younger compared to the older patients, both suggest a significant mortality risk during childhood for patients with severe disease.
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影响因子：
1.9
作者：
Opladen, Thomas;Cortes-Saladelafont, Elisenda;Mastrangelo, Mario;Horvath, Gabriella;Pons, Roser;Lopez-Laso, Eduardo;Fernandez-Ramos, Joaquin A.;Honzik, Tomas;Pearson, Toni;Friedman, Jennifer;Scholl-Buergi, Sabine;Wassenberg, Tessa;Jung-Klawitter, Sabine;Kuseyri, Oya;Jeltsch, Kathrin;Kurian, Manju A.;Garcia-Cazorla, Angels
通讯作者：
Garcia-Cazorla, Angels
芳香族l-氨基酸脱羧酶（AADC）缺乏症诊断和治疗共识指南。
影响因子：
3.7
作者：
Wassenberg T;Molero-Luis M;Jeltsch K;Hoffmann GF;Assmann B;Blau N;Garcia-Cazorla A;Artuch R;Pons R;Pearson TS;Leuzzi V;Mastrangelo M;Pearl PL;Lee WT;Kurian MA;Heales S;Flint L;Verbeek M;Willemsen M;Opladen T
通讯作者：
Opladen T
DOI：
10.1007/8904_2017_54
发表时间：
2018-01-01
期刊：
JIMD REPORTS, VOL 40
影响因子：
--
作者：
Hwu, Wuh-Liang;Chien, Yin-Hsiu;Li, Mei-Hsin
通讯作者：
Li, Mei-Hsin
影响因子：
14.5
作者：
Kojima, Karin;Nakajima, Takeshi;Yamagata, Takanori
通讯作者：
Yamagata, Takanori
影响因子：
9.9
作者：
Brun, L.;Ngu, L. H.;Blau, N.
通讯作者：
Blau, N.