苯丙酮尿症患儿脑髓鞘发育延迟与血苯丙氨酸浓度关系的研究

Study on brain delayed myelination and blood phenylalanine of patients with phenylketonuria

目的应用MRI观察苯丙酮尿症（PKU）患儿脑髓鞘发育延迟与血苯丙氨酸（PHE）浓度的关系。方法对2002—2004年北京中日友好医院PKU门诊确诊的经典型PKU患儿29例,治疗前进行头颅MRI及血苯丙氨酸浓度检查,脑髓鞘发育按Staudt标准对不同年龄阶段患儿脑10个区域进行量化评估。HPLC法定量测定血PHE浓度。根据开始接受治疗年龄不同分为甲（28~48周,11例）、乙（49~390周,18例）两组,另随机选取其中19例治疗1年后复查MRI进行治疗前后对照,根据该19例治疗中血苯丙氨酸浓度控制情况分为A组（血PHE控制在0.12~0.48mmol/L）和B组（血PHE控制在0.12~0.48mmol/L以外）。结果29例患儿治疗前均存在髓鞘发育延迟,在10个脑区域髓鞘发育延迟平均发生率为45.6%,主要部位在脑叶和胼胝体,其中甲组髓鞘发育延迟平均发生率为40.8%,乙组发生率为51.2%,甲乙组间差异有显著性意义（P〈0.05）;经低苯丙氨酸饮食治疗1年后,19例10个脑区域髓鞘发育延迟平均发生率为32.2%;治疗前后髓鞘延迟有显著性改善（P〈0.01）,且治疗中血PHE浓度控制较好的A组髓鞘延迟改善率为1.75±0.66,B组病例为0.78±0.44,差异有显著性（P〈0.01）,髓鞘延迟改善与血PHE浓度间有密切相关性。结论治疗延迟的PKU患儿的脑髓鞘发育延迟的高发病率,与高血PHE浓度影响时间有关;经低苯丙氨酸饮食治疗延迟的改善率,与治疗中血PHE浓度控制情况直接影响延迟改善,因此提示PKU患儿血PHE浓度是影响脑髓鞘发育延迟发生及改善的重要原因。

Objective To observe the relationship between phenylalanine and brain delayed myelination in phenylketonuria （ PKU ） with MRI. Methods All of 29 PKU patients underwent cranial MR imaging with spin-echo T1-weighted and T2-weighted sequences in coronal and axial planes. The myelination in ten sections was evaluated by using MRI T1 and T2WI with Staudt＇s staging system. Results All of the 29 patients with PKU had aniso degree delayed myelination on MRI. Delayed myelination was located mainly in the cerebral lobes and corpus callosum, the incidence of sections of delayed myelination was 45. 6% ,the incidence of low age was 40. 8% and the high age group was 51.2% ,showing statistically significant change （ P 〈0.05 ）. After a year of treatment with a PHE-restricted diet,the incidence in the 19 patients was 32. 2% ,showing statistically significant change （ P 〈 0. 01 ）. The largest change in MRI was seen in patients who controled PHE level around 0. 12 -0. 48mmol/L. Conclusion The patients,with delayed treated PKU have a high occurrence of delayed brain myelination, and the longer the high blood PHE level, the worse the delayed brain myelination. Throuth the therapy with a PHE-restricted diet, these abnormalities can be improved, and amelioration of the delayed myelination is much better in the group who controled PHE level around O. 12 -0. 48mmol/L. This level of blood PHE is the main reason responsible for the delayed myelination.