论文部分内容阅读
目的 探讨 6 丙酮酰四氢蝶呤合成酶 (6 pyruvoyltetrohydropterinsynthase ,PTPS)缺乏所致四氢生物蝶呤 (tetrahydrobiopterin ,BH4)缺乏症的诊断、治疗与产前诊断方法。 方法 10例患儿 (男 2例、女 8例 )均经血苯丙氨酸、尿蝶呤谱分析诊断。 7例患儿及其父母接受了PTPS基因检测 ,其中 2个家系通过羊水细胞基因分析对胎儿作了诊断。 结果 10例血苯丙氨酸不同程度增高 ,尿生物蝶呤显著降低 ,符合PTPS缺乏症。其中 7例未接受新生儿筛查 ,于婴儿早期出现进行性神经系统损害 ,来院时智力损害严重 ,6例合并惊厥及营养不良 ,5例呈松软儿状态 ,2例肌张力不全 ,6例分别于 2岁半～ 6岁死亡。 3例为新生儿疾病筛查发现 ,其中 2例曾接受低苯丙氨酸奶粉治疗无效 ,经BH4、左旋多巴、5 羟色氨酸等治疗后逐渐好转。 1例自出生 1个月起开始治疗 ,智力运动发育良好。7个家系接受了PTPS基因分析 ,分别发现了 15 5A >G、2 2 6C >T、2 5 6C >T、2 5 9C >T、2 72A >G、2 86G>A、317C >T、IVS3+1G >A、IVS1 2 91A >G ,共 9种基因突变。完成产前诊断的 2个家系中的第 3个胎儿都排除了PTPS缺乏症 ,出生后再次验证 ,发育正常。 结论 PTPS缺乏症是导致BH4缺乏症的主要原因 ,早期诊断、正确治疗是挽救患儿的关键。建议?
Objective To investigate the diagnosis, treatment and prenatal diagnosis of tetrahydrobiopterin (BH4) deficiency induced by 6 pyruvoyltetrahydropterin synthase (PTPS) deficiency. Methods 10 cases of children (2 males and 8 females) were diagnosed by blood phenylalanine, urinary pterin spectrum analysis. Seven children and their parents underwent PTPS genetic testing, and two of the families diagnosed the fetus by amniotic fluid cell genetic analysis. Results 10 cases of blood phenylalanine increased to varying degrees, urine biopterin significantly reduced, in line with PTPS deficiency. Seven of them did not undergo neonatal screening. They had progressive neurological damage in early infancy, severe mental impairment at admission, convulsions and malnutrition in 6 patients, floppy in 5, hypertonia in 2, and dystonia in 6 At 2 years old to 6 years old died. Three cases of neonatal disease screening found that two of them had received low phenylalanine milk powder treatment ineffective, by BH4, levodopa, 5-hydroxytryptophan and other treatment gradually improved. One case started treatment from 1 month after birth and the mental activity developed well. 7 families received PTPS gene analysis and found 15 5A> G, 226C> T, 256C> T, 259C> T, 72A> G, 286G> A, 317C> T, IVS3 + 1G> A, IVS1 2 91A> G, a total of 9 kinds of gene mutations. The third fetus in both families who completed prenatal diagnosis ruled out PTPS deficiency and was re-validated after birth with normal development. Conclusions PTPS deficiency is the main cause of BH4 deficiency. Early diagnosis and correct treatment are the keys to saving children. Suggest?