AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.,Journal of Inherited Metabolic Disease

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AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.
Journal of Inherited Metabolic Disease ( IF 4.2 ) Pub Date : 2020-05-05 , DOI: 10.1002/jimd.12247
Toni S Pearson ₁ , Laura Gilbert ₁ , Thomas Opladen ₂ , Angeles Garcia-Cazorla ₃ , Mario Mastrangelo ₄ , Vincenzo Leuzzi ₄ , Stacy K H Tay ₅ , Jolanta Sykut-Cegielska ₆ , Roser Pons ₇ , Saadet Mercimek-Andrews ₈ , Mitsuhiro Kato ₉ , Thomas Lücke ₁₀ , Mari Oppebøen ₁₁ , Manju A Kurian ₁₂ , Dora Steel ₁₂ , Filippo Manti ₄ , Kathleen D Meeks ₁ , Kathrin Jeltsch ₂ , Lisa Flint ₁₃

Affiliation

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Division of Child Neurology & Metabolic Medicine, University Children's Hospital, Heidelberg, Germany.
Inborn Errors of Metabolism Unit, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain.
Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
KTP-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
Department of Inborn Errors of Metabolism and Pediatrics, Institute of Mother and Child, Warsaw, Poland.
First Department of Pediatrics, Aghia Sofia Hospital, University of Athens, Athens, Greece.
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
University Children's Hospital, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
Division of Child Neurology, Oslo University Hospital, Oslo, Norway.
Developmental Neurosciences, UCL Great Ormond Street-Institute of Child Health and Department of Neurology, Great Ormond Street Hospital, London, UK.
AADC Research Trust, Caterham, UK.

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.

中文翻译：

从婴儿期到成年期的 AADC 缺乏症：63 名患者的国际队列的症状和发育结果。

芳香升氨基酸脱羧酶缺乏症 (AADCD) 是一种罕见的常染色体隐性神经发育障碍，其特征是多巴胺、去甲肾上腺素、肾上腺素和血清素的合成受损，导致复杂的运动、行为和自主症状综合征。这项回顾性研究通过医生和/或护理人员对详细、标准化问卷的回应，评估了大型国际 AADCD 患者队列的症状和发育结果。来自 23 个国家的 63 名患者（60% 女性；年龄 6 个月至 36 岁，中位年龄 7 岁；58 人在世）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）是张力减退、发育迟缓和/或眼科危象。97% 的 2 至 12 岁患者存在眼科危象，发生在所有年龄组的大多数患者中，并且往往在儿童早期最为严重。突出的非运动症状是睡眠障碍、情绪烦躁和喂养困难。大多数受试者 (70%) 有严重的运动障碍，其特征是缺乏头部控制和极少的自主运动，而 17% 有轻度运动障碍并且能够独立行走。多巴胺激动剂是最有可能产生一些症状益处的药物，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% 的受试者在 13 岁以下），并且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大，

更新日期：2020-05-05

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