摘要
目的探讨中国北方人群四氢生物蝶呤(tetrahydrobiopterin,BH4)缺乏症的筛查、治疗和长期预后。方法自1992年到2005年,我院共诊治主要来自中国北方地区的高苯丙氨酸血症(hyperpheny lalaninemia,HPA)患者618例。采用尿蝶呤谱分析,红细胞二氢蝶啶还原酶(dihydropteridinereductase,DHPR)活性测定及四氢生物蝶呤负荷试验,对这些患者进行BH4缺乏症的鉴别诊断;确诊患者立即进行BH4、左旋多巴和5羟色胺三药联合治疗。定期随诊患者的精神运动和智能发育情况。结果(1)在618例HPA患者中,共鉴别出38例BH4缺乏症,而且皆表现为尿生物蝶呤显著降低,新蝶呤显著增加,红细胞DHPR活性正常,血苯丙氨酸浓度在BH4负荷后4～8小时内降至正常,即全部是6丙酮酰四氢蝶呤合成酶(6pyruvoyl tetrahydropterinsynthase,PTPS)缺乏型,被确诊时的年龄为2岁零1个月～13岁;(2)其中,只有27例患儿接受规律治疗并定期随诊。在经过3个月～10年的治疗后,患者的发育商或智商(developmentorintelligence quotient,DQ/IQ)明显提高(治疗前后分别为52±16,79±15),但智能发育各个方面并不平行;(3)通过对患儿目前DQ/IQ与治疗开始时间进行Pearson相关分析发现,二者呈明显负相关(r=-0.714,P<0.01)。结论对所有HPA患者都必须早期进行BH4缺乏症的鉴别诊断;PTPS缺乏症是中国北方导致BH4缺乏症的主要原因;PTPS缺乏症患者必须进行BH4、左旋多巴和5羟色胺三药联合治疗,而且治疗越早,效果越好。
Objective To emphasize early differential diagnosis from patients with hyperphenylalaninemia （HPA） and to evaluate the treatment and long-term outcome of patients with tetrahydrobiopterin synthase （BH4） deficiency in Northern Chinese population. Methods From 1992 to 2005, a total of 618 patients with HPA were diagnosed and/or cared for in our outpatient clinic. Urinary pterin analysis, detection of dihydropteridine reductase （DHPR） activity in blood, and then BH4 loading tests were carried out to differentiate BH4 deficiency in these patients from classical phenylketonuria. BH4 deficient patients were treated with BH4, hvodopa and 5-hydroxytryptophane （5-HTP） immediately while the diagnosis was done to disease. Patients＇ blood phenylalanine levels, psychomotor and intelligence development were followed up. Results A total of 38 cases were diagnosed as BH4 deficiency, all of them were revealed as 6-pyruvoyl-tetrahydropterin synthase （FFPS） deficiency from the extremely decreased urine biopterin, normal DHPR activities and drop down of blood phenylahnine level to normal range within 4 to 8 hours after BH4 loading, the most conanon manifestations were progressively psychomotor and mental retardation to patients even after taking early dietary treatment. The patients were diagnosed and treated with drugs at the ages of 2.1 months to 13 years. With 4 patients died of pneumonia, 7 patients refused to treatment, only 27 patients were under treatment and followed up. The average full scale development or intelligence quotient （DQ/IQ） of patients who were treated within and after 6 months were 86± 10 or 66± 7 respectively. Development was not even in different aspects. A significant negative correlation was observed between the level of the DQ and the age of treatment commenced （ r = - 0. 714, P 〈 0.01）. Eleven patients experienced the extrapyrsmidal movement disorders, 3 of them combined with epilepsy. The extrapyramidal disorders were controlled by administration of levodopa. Conclusion The differential diagnosis for BH4 deficiency should be carded out in all patients with HPA. FFPS deficiency is the most common form of BH4 deficiency in Northern Chinese population. The long-term outconme of these patients benefits from diagnosis and treatment with BH4, levodopa and 5-HTP as early as possible.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2006年第3期275-279,共5页
Chinese Journal of Medical Genetics
基金
国家自然科学基金(30271372)~~
