Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Paediatric Neurology (820 IKNC), PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Brain. 2010 Jun;133(Pt 6):1810-22. doi: 10.1093/brain/awq087. Epub 2010 Apr 29.
Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.
酪氨酸羟化酶缺乏症是一种常染色体隐性疾病，导致脑儿茶酚胺缺乏。全球报道的病例少于 40 例。为了总结这种破坏性但可治疗的神经代谢疾病的所有现有临床表型和合理的诊断及治疗方法的证据，我们研究了 36 例酪氨酸羟化酶缺乏症患者，并复习了文献。根据临床表现，酪氨酸羟化酶缺乏症可分为两种表型：一种是婴儿起病、进行性、少动性僵硬伴肌张力障碍（A型），另一种是伴有新生儿起病的复杂脑病（B 型）。脑脊液中高香草酸和 3-甲氧基-4-羟基苯乙二醇浓度降低，而 5-羟吲哚乙酸脑脊液浓度正常，是酪氨酸羟化酶缺乏症的生化特征。脑脊液中高香草酸浓度和高香草酸/5-羟吲哚乙酸比值与表型严重程度相关。酪氨酸羟化酶缺乏症几乎完全由 TH 基因及其启动子区域的错义突变引起，这表明对蛋白质具有更具破坏性影响的突变与生命不相容。常见的 c.698G>A 和 c.707T>C 突变不存在基因型-表型相关性。然而，至少携带一个启动子突变的携带者显然预测为 A 型酪氨酸羟化酶缺乏症。大多数酪氨酸羟化酶缺乏症患者可以用左旋多巴成功治疗。
