Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of Dopamine and Serotonin Synthesis
Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of Dopamine and Serotonin Synthesis
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DOI：
10.1007/8904_2014_327
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Pearl, Phillip L.
中科院分区：
文献类型：
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作者：
Helman, Guy;Pappa, Maria Belen;Pearl, Phillip L.
目的：芳香族氨基酸脱羧酶缺乏症表现为突出的锥体外系和自主神经特征，CSF单胺缺乏症表现为3-O-甲基多巴（L-多巴累积的副产物）增加。已查明的病例不到100例。该疾病通常与严重的表型和女性预后不良相关。基因转移技术已实施使用腺相关病毒编码AADC在壳bilaterals.Methods：我们描述的表型/基因型在一个队列中的5例表现出异质性表型和完整的反应，以药理学therapy.Results：5例（年龄范围2-10年，平均5年，3 M/2F）与确认AADC缺陷。4例（3例M/1例F）患者在多巴胺能激动剂、MAO抑制剂、吡哆醇/P5 P和亚叶酸联合治疗后改善。每个人都表现为张力减退、自主运动减少、肌张力障碍、易怒和眼球旋转危象。2例（1例男性/1例女性）可独立行走，不依赖胃造口管喂养; 9岁女孩可阅读单个单词。一只雌性动物具有重度表型，包括与心动过缓相关的复发性低血糖事件，尽管后者已通过长期抗胆碱能治疗消退。一个台湾男孩有共同的纯合突变，否则我们描述了五个新的DDC mutations.Conclusions：我们报告了一个更广泛的表型谱，包括完整的反应，药物管理和温和的结果在女性，以及五个新的突变。五名患者中有四名在联合治疗后有所改善，包括多巴胺激动剂，MAO抑制剂，吡哆醛-50-磷酸盐和亚叶酸。病毒介导的AADC缺陷基因治疗的出现使得对结果的扩展知识变得越来越重要。
Objectives: Aromatic amino acid decarboxylase deficiency presents with prominent extrapyramidal and autonomic features and CSF monoamine deficiency with increased 3-O-methyldopa, a by-product of accumulated L-DOPA. Less than 100 cases have been identified. The disease is typically associated with a severe phenotype and worse prognosis in females. Gene transfer technology has been implemented using an adeno-associated virus encoding AADC in the putamen bilaterally.Methods: We describe the phenotype/genotype in a cohort of five cases showing a heterogeneous phenotype and variably intact response to pharmacologic therapy.Results: Five patients (age range 2-10 years, mean 5 years, 3M/2F) with confirmed AADC deficiency are described. Four (3M/1F) have had improvement on combinations of dopaminergic agonists, MAO inhibitors, pyridoxine/P5P, and folinic acid. Each presented with hypotonia, decreased voluntary movement, dystonia, irritability, and oculogyric crises. Two (1M/1F) are independently ambulatory and are not dependent on gastrostomy tube feedings; the 9-year-old girl is reading single words. One female has a severe phenotype including recurrent hypoglycemic events associated with bradycardia, although the latter have resolved with chronic anticholinergic therapy. One Taiwanese boy had the common homozygous mutation, and otherwise we describe five new DDC mutations.Conclusions: We report a wider phenotypic spectrum including intact response to pharmacologic management and milder outcome in a female, as well as five new mutations. Four of five patients have improved on combination therapy including a dopamine agonist, MAO inhibitor, pyridoxal-50-phosphate, and folinic acid. The advent of viral-mediated gene therapy in AADC deficiency renders expanded knowledge of the outcome increasingly important.