Helman Guy, Pappa Maria Belen, Pearl Phillip L
Department of Neurology, Children's National Medical Center, Washington, DC, USA.
JIMD Rep. 2014;17:23-7. doi: 10.1007/8904_2014_327. Epub 2014 Jul 8.
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.
We describe the phenotype/genotype in a cohort of five cases showing a heterogeneous phenotype and variably intact response to pharmacologic therapy.
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.
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-5'-phosphate, and folinic acid. The advent of viral-mediated gene therapy in AADC deficiency renders expanded knowledge of the outcome increasingly important.
芳香族氨基酸脱羧酶缺乏症表现为明显的锥体外系和自主神经特征，脑脊液单胺缺乏，同时3 - O - 甲基多巴增加，3 - O - 甲基多巴是蓄积的左旋多巴的一种副产物。已确诊的病例不到100例。该疾病通常与严重的表型相关，女性预后更差。已使用腺相关病毒在双侧壳核中编码芳香族氨基酸脱羧酶来实施基因转移技术。
我们描述了一组5例患者的表型/基因型，这些患者表现出异质性表型以及对药物治疗的反应各不相同。
描述了5例确诊为芳香族氨基酸脱羧酶缺乏症的患者（年龄范围2 - 10岁，平均5岁，3男/2女）。4例（3男/1女）在多巴胺能激动剂、单胺氧化酶抑制剂、吡哆醇/磷酸吡哆醛和亚叶酸联合使用后病情有改善。每位患者均表现为肌张力低下、自主运动减少、肌张力障碍、易激惹和动眼危象。2例（1男/1女）能够独立行走，不依赖胃造瘘管喂养；这位9岁女孩能够认读单个单词。一名女性有严重的表型，包括与心动过缓相关的反复低血糖事件，不过后者通过长期抗胆碱能治疗已得到缓解。一名台湾男孩有常见的纯合突变，此外我们还描述了5种新的DDC突变。
我们报告了更广泛的表型谱，包括对药物治疗有良好反应以及一名女性病情较轻的情况，还有5种新突变。5例患者中有4例在包括多巴胺激动剂、单胺氧化酶抑制剂、磷酸吡哆醛 - 5'- 磷酸和亚叶酸的联合治疗后病情有所改善。在芳香族氨基酸脱羧酶缺乏症中，病毒介导的基因治疗的出现使得对治疗结果的更广泛了解变得日益重要。
