不同类型高苯丙氨酸血症的临床表型

Clinical Phenotype of Different Hyperphenylalaninemia Patients

目的探讨不同类型高苯丙氨酸血症（HPA）临床表型,了解HPA患者对低苯丙氨酸（Phe）饮食治疗的反应性。方法HPA患儿44例均口服四氢生物喋呤（BH4）负荷试验（20 mg/kg）或Phe-BH4联合负荷试验,同时进行尿喋呤谱分析、红细胞二氢喋呤还原酶（DHPR）测定。治疗前采用Gesell发育量表进行智力测定并行脑电图检查。予苯丙氨酸羟化酶（PAH）缺乏症患者低Phe饮食治疗,控制血Phe在120~360μmol/L,监测Phe耐受量。结果1.确诊BH4反应性PAH缺乏症患儿12例。男7例,女5例;平均年龄7.8个月;生化代谢表型均为轻度或中度HPA。2.部分BH4缺乏症患儿确诊前经低Phe饮食治疗后血Phe可以控制在较低水平,但仍出现进行性神经损害,脑电图异常率为72.7%。3.BH4反应性PAH缺乏症的发育商明显高于其他HPA;饮食治疗中的Phe耐受量较高。结论BH4反应性PAH缺乏症患者对饮食治疗的反应性更好。早期BH4缺乏症的鉴别诊断非常重要。

Objective To explore clinical characteristics of phenylalanine hydroxylase （PAH） deficiency in differential diagnosis among hy- perphenylalaninemia （HPA） patients and compare the responses to diet treatment in HPA patients. Methods Tetrabydrobiopterin （ BH4 ,20 mg/ kg） loading test or combined phenylalanine （Phe, 100 mg/kg） and B H4 loading test was carried out among 44 HPA patients. The urine pterine profile analysis and dihydropteridine redudtase （DHPR） activity in dry blood filter spot were analyzed simultaneously. Electroencephalogram （EEG） and average full scale development quotient （DQ） were performed in all patients. PAIt deficiency patients were given low Phe diet treatment to decrease Phe level for 120 -360 μmol/L and followed up their Phe tolerance. Results Twelve BH4 responsive PAH deficiency patients were diagnosed who were 7 males and 5 females, mean age was 7.8 months. Their metabolic phenotype was moderate or mild HPA. Diet control could decrease Phe level among BH4 deficiency patients but not prevent their neural damage and their EEG abnormal rate was higher. BH4 responsive patients had higher DQ than others and their Phe tolerance increased during diet treatment. Conclusions BH4 responsive PAH deficiency patients can obtain better purpose with diet recipe. The differential diagnosis for BH4 deficiency shall be carried out in all patients with HPA as soon as possible.