酪氨酸羟化酶缺乏症导致的多巴反应性肌张力不全一例临床特点及基因检测

Tyrosine hydroxylase deficiency： a case of autosomal recessive dopa-responsive dystonia

目的分析酪氨酸羟化酶缺乏症导致的多巴反应性肌张力障碍患儿临床特征及基因突变，探讨其分子遗传学机制。

Objective To analyze the clinical characteristics of the patient with tyrosine hydroxylase deficiency, and investigate it＇s molecular mechanism. Method The clinical characteristics of a patient with tyrosine hydroxylase deficiency were summarized and analyzed, his and his family＇s peripheral blood specimens were collected after informed consent was signed. All exons and the intron-exon boundaries of guanosine triphosphate hydroxylase I gene, tyrosine hydroxylase gene and sepiapterin reductase gene were examined by DNA-PCR, hi-directional sequencing. Result The patient was a 3-year-old boy, presented with unexplained dystonia for 3 years, without significant impairment of intelligence. Physical examination showed limb muscle strength grade V, rigidity of extremities, hypertonicity, brisk deep tendon reflexes in limbs, without obvious abnormalities in auxiliary examination, such as brain MRI, hepatic biochemical panel, creatine kinase, and cerulop｜asmin. He dramatically responded to small doses of levodopa in the follow-up for half a year. A homozygous missense change in exon 5 of TH gene, c. 605G 〉 A （ p. R202H）, which was a known pathogenic mutation, was found in the patient. His parents were heterozygous for the R202H mutation. Conclusion The age of onset in tyrosine hydroxylase deficiency patients is usually within the first year of life. Unexplained dystonia and hypokinesia were the main clinical features of tyrosine hydroxylase deficiency. The dopa-responsive effects for some patients are so obvious that we should strengthen awareness of the disease. TH gene c. 605G 〉 A （ p. R202H） may be a common type of causative mutations for the mild form at home and abroad.