Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency
Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency
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DOI：
10.1212/wnl.0b013e3181e620ae
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发表时间：
2010-07-06
期刊：
影响因子：
9.9
通讯作者：
Blau, N.
中科院分区：
文献类型：
--
作者：
Brun, L.;Ngu, L. H.;Blau, N.
目的：描述芳香族L氨基酸脱羧酶缺乏症患者的治疗现状、临床、生化和分子生物学表现以及临床随访情况。方法：将78例芳香族氨基酸脱羧酶缺乏症患者的临床和生化资料纳入儿童神经递质紊乱病数据库。结果：在96%的AADC缺陷患者中，95%的患者在婴儿期或儿童期出现明显的临床症状(95%的患者出现低眼压，86%的患者出现眼肌危象，63%的患者出现发育迟缓)。实验室诊断依据是典型的脑脊液标志物(低高香草酸、5-羟基吲哚酸和3-甲氧基-4-羟基苯甘醇，3-O-甲基-L-多巴、L-多巴和5-羟色氨酸)，缺乏血浆AADC活性，或尿香草酸升高。在49例患者中共检测到24个DDC基因突变(其中8个为首次报道：p.L38P、p.Y79C、p.A110Q、p.G123R、p.I42fs、c.876G>；A、p.R412W、p.I433fs)，其中以IVS6+4A>；T最为常见(等位基因频率为45%)。结论：脑脊液神经递质谱对芳香族L氨基酸脱羧酶缺乏症的诊断具有重要意义。治疗选择有限，在许多情况下无益，预后不确定。只有15名病情相对较轻的患者在吡哆醇(B6)/磷酸吡哆醛、多巴胺激动剂和单胺氧化酶B抑制剂的联合治疗下明显改善。《神经病学》(R)2010；75：-71
Objective: To describe the current treatment; clinical, biochemical, and molecular findings; and clinical follow-up of patients with aromatic L-amino acid decarboxylase (AADC) deficiency.Method: Clinical and biochemical data of 78 patients with AADC deficiency were tabulated in a database of pediatric neurotransmitter disorders (JAKE). A total of 46 patients have been previously reported; 32 patients are described for the first time.Results: In 96% of AADC-deficient patients, symptoms (hypotonia 95%, oculogyric crises 86%, and developmental retardation 63%) became clinically evident during infancy or childhood. Laboratory diagnosis is based on typical CSF markers (low homovanillic acid, 5-hydroxyindoleacidic acid, and 3-methoxy-4-hydroxyphenolglycole, and elevated 3-O-methyl-L-dopa, L-dopa, and 5-hydroxytryptophan), absent plasma AADC activity, or elevated urinary vanillactic acid. A total of 24 mutations in the DDC gene were detected in 49 patients (8 reported for the first time: p.L38P, p.Y79C, p.A110Q, p.G123R, p.I42fs, c.876G>A, p.R412W, p.I433fs) with IVS6+4A>T being the most common one (allele frequency 45%).Conclusion: Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic L-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors. Neurology (R) 2010; 75: 64-71