苯丙酮尿症研究十八年

将自1984年以来在中日友好医院开展的有关苯丙酮尿症(PKU)的主要研究工作总结如下：(1)1984年10月-2002年9月，共诊治苯丙酮尿症(PKU)患者603例。经新生儿筛查发现并在出生后3个月内开始治疗者136例，195例在3-12个月时就诊，272例1岁以上就诊。晚发现的467例PKU患者均有PKU的症状和体征，119例合并癫痫。经低苯丙氨酸饮食治疗，早治患者的智能和体格发育正常，晚治者的异常行为明显改善、智能也有不同程度提高。22个PKU家庭作了产前基因诊断，防止了第二胎患病胎儿的出生。(2)采用高效液相色谱仪(HPLC)对369例高苯丙氨酸血症(HPA)患者进行尿液喋呤测定，22例诊断为四氢生物喋呤(BH4)缺乏症。对18例BH4缺乏症患者及其家系进行基因分析，发现6种基因突变，其中259C→T和286G→A为中国北方人的常见突变。18例患者接受了BH4、L—多巴及5—羟色胺联合治疗，疗效满意。(3)未经治疗的PKU患者的脑电图(EEG)及颅脑磁共振成像(MRI)异常均具有高发生率。脑电图异常所见主要为痫样放电，少数为背景活动异常。颅脑MRI异常以T2WI上脑白质内散在斑片高信号灶最为常见，其次为脑髓鞘化发育延迟及脑发育不良。经低苯丙氨酸饮食治疗后，绝大多数患者脑电图及脑MRI随之改善。(4)将29例晚治的经典型PKU患者的基因型与治疗前的智能障碍程度作一比较，22例基因型与智力表型相符，7例不符，提示晚治PKU患者的基因型与其治疗前的智力表型有较好的一致性。

An eighteen-year study on phenylketonuria

A study on phenylketonuria (PKU) has been carried out in China-Japan Friendship Hospital since 1984. The results revealed that: (1) Totally 603 patients with PKU were diagnosed and treated in the hospital from October 1984 to September 2002. Among which 136 cases were identified by neonatal screening and treated within 3 months. One hundred and ninety-five cases were treated when the children were 3-12 months of age. Another 272 PKU children were diagnosed when they were more than 1 year old. All of these late-treated cases had some signs and symptoms of PKU. Mental retardation was found in 467 cases and various patterns of seizures in 119 cases. After treatment with low-phenylalanine diet, the follow-up for early-treated patients revealed that their physical and mental developments were normal. In late-treated patients, abnormal behaviour was significantly improved and their developmental quotient were elevated. Prenatal gene diagnosis of PKU risk foetus in 22 PKU families was successfully performed. (2) Urinary pterins obtained from 369 HPA patients were measured by HPLC. Twenty two patients with BH4 deficiency have been recognized. Six single base mutations were detected in 18 unrelated northern Chinese BH4 deficiency families, and the mutations at nucleotides 259C-->T and 286G-->A were common mutations. Eighteen BH4 deficient patients were treated with BH4, L-dopa and 5-hydroxytryptophan, and the results were satisfactory. (3) The abnormal rate of EEG was high in untreated patients with PKU, mainly showing epileptiform discharges and partly showing background activity abnormality. The most frequent finding was patchy areas of increased signal intensity in white matter on MRI in the brain of PKU patients, while delayed myelination and brain agenesis were often detected. After dietary treatment, follow-ups with EEG and MRI revealed that the abnormalities were decreased significantly. (4) The relationship between genotype and intellectual phenotype was examined in 29 late-treated patients with classical PKU. It was found that the genotype of 22 patients were compatible with intellectual phenotype and not well matched in 7 cases. The result indicate that the genotype was well matched with intellectual phenotype in classical PKU patients.