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目的探讨四氢生物蝶呤反应性苯丙氨酸羟化酶(PAH)缺乏症这一新的临床变异型在高苯丙氨酸血症(HPA)中的发生率,并进一步了解其PAH基因突变类型。方法2001年1月至2004年12月,上海第二医科大学附属新华医院收治的106例中位年龄2个月(0.5～59个月)的HPA患儿纳入研究。所有患儿做辅酶的羟生物蝶呤(BH4,20mg/kg)或联合血苯丙氨酸(Phe,100mg/kg)负荷试验、尿蝶呤谱分析及红细胞二氢蝶啶还原酶活性(DHPR)测定。以口服BH4后24h内血Phe浓度下降30%以上且排除BH4缺乏症为诊断标准。对13例BH4反应性PAH缺乏症患儿进行PAH基因突变检测。结果106例HPA者中41例(38.7%)为BH4反应性的PAH缺乏症。血Phe浓度在服用BH4前为(816±431)μmol/L,服BH4后24h内降至(267±198)μmol/L,反应下降率(67±19)%。41例尿蝶呤及DHPR活性均正常。106例中轻度HPA(18例)其BH4反应性PAH缺乏症发生率为61.1%(11/18)。13例做PAH基因突变检测,R241C为最多见突变类型(43.8%)。结论61.1%轻度HPA(11/18)及42.4%(28/66)轻度PKU对BH4有较大反应性。BH4负荷试验是该病有效而简便的鉴别诊断方法。
Objective To investigate the incidence of tetrahydrobiopterin reactive phenylalanine hydroxylase (PAH) deficiency in hyperphenylalaninemia (HPA) and to further understand its PAH gene Mutation type. Methods From January 2001 to December 2004, 106 children aged 2 months (0.5 to 59 months) with HPA admitted to Xinhua Hospital affiliated to Shanghai Second Medical University were enrolled in the study. All patients were tested for hydroxybipate (BH4, 20 mg / kg) or combined with Phe (100 mg / kg) coenzyme, urinary pterin analysis and DHPR activity ). Within 24 hours after oral BH4 blood Phe concentration decreased by more than 30% and exclude BH4 deficiency as the diagnostic criteria. PAH gene mutation was detected in 13 children with BH4-responsive PAH deficiency. Results Of the 106 HPA cases, 41 (38.7%) were BH4-reactive PAH deficiency. The blood Phe concentration was (816 ± 431) μmol / L before taking BH4, and dropped to (267 ± 198) μmol / L within 24 h after taking BH4. The rate of decline of reaction was (67 ± 19)%. 41 cases of urinary excretion and DHPR activity were normal. The incidence of BH4-reactive PAH deficiency was 61.1% (11/18) in 106 mild cases of HPA (18 cases). 13 cases of PAH gene mutation detection, R241C is the most common type of mutation (43.8%). Conclusions 61.1% mild HPA (11/18) and 42.4% (28/66) mild PKU are more responsive to BH4. BH4 load test is a valid and simple differential diagnosis of the disease.