4羟基丁酸尿症6例临床及实验室研究

The clinical and laboratory research of 4-hydroxy butyrate aciduria in 6 cases.

目的探讨4羟基丁酸尿症患儿临床特征及实验室诊断方法。方法2012年6月至2013年6月天津市儿童医院收治的6例4羟基丁酸尿症患儿，应用头磁共振成像（MRI）、尿气相色谱一质谱（GC／MS）半定量检测及ALDH5A1基因突变分析多层面分析。结果6例均存在精神运动发育落后。3例存在癫痫发作。5例起病年龄〈1岁。4例头MRI示双侧对称性苍白球病变。6例尿GC／MS半定量检测示尿4羟基丁酸与内标比值增高（1252．4—9059．8）；ALDH5A1基因突变分析示不同位点均可出现突变（2例为c．1568C〉T纯合突变，余4例分别为c．691G〉A，c．1568C〉T；IVS9—2delA，C．1568C〉T；c．527G〉A，c．691G〉A；c．904G〉A，O．1022C〉A复合杂合突变）。结论头MRI双侧对称性苍白球病变是本病影像学特征。尿GC／MS为本病诊断依据。ALDH5A1基因不同位点均可发生突变，为本病基因诊断依据。

Objective To study the clinical features of 4-hydroxy butyrate aciduria and the laboratory diagnostic methods.Methods From June 2012 to June 2013,6 cases in Tianjin Children＇s Hospital were analyzed.Head MRI ,urine GC/ MS semiquantitative testing and gene mutation analysis of ALDHSA1 were used to analyze 4-hydroxy butyrate aciduria diagnosis.Result All of the six cases had psychomotor retardation, three of them with epileptic seizures, five of them with onset before 1 year old;four cases showed Head MRI bilateral symmetry pallidal lesions.By the urine GC/MS semi- quantitative testing, six cases showed that 4-hydroxy butyric acid and Internal standard ratio increased （1252.4 9059.8）.By the ALDHSA1 gene mutation analysis, six cases showed that in different positions all of them could mutate （2 cases belonging to c.1568C 〉 T homozygous mutation, the other 4 cases belonging to compound heterozygous muta- tion,which included c.691G 〉 A, c. 1568C 〉 T; IVS9-2delA, c. 1568C 〉 T; c.527G 〉 A, c.691G 〉 A; c.904G 〉 A, c. 1022C 〉 A）. Conclusion The head MRI bilateral symmetry pallidal lesions is the specific feature of the disease imaging; urine GC/ MS is the basis of the disease; ALDHSA1 gene can mutate in different positions, which is the basis of this disease.