ABNORMAL-METABOLISM OF VALPROIC ACID IN FATAL HEPATIC-FAILURE
ABNORMAL-METABOLISM OF VALPROIC ACID IN FATAL HEPATIC-FAILURE
复制标题
DOI：
10.1007/bf00445664
复制
发表时间：
1983-01-01
影响因子：
3.6
通讯作者：
RITZ, A
中科院分区：
文献类型：
--
作者：
KOCHEN, W;SCHNEIDER, A;RITZ, A
一名7岁男孩在5岁时出现严重的单侧癫痫发作(苯巴比妥治疗)；1.5岁后加入丙戊酸(2-丙基戊酸，VPA)治疗。在3个月的无癫痫发作后。患者死于肝功能衰竭REEY综合征。用气相色谱/质谱仪(GC/MS)分析腹膜透析前和腹膜透析过程中终末期的几份血浆和尿样。主要特征是血浆中VPA的3种单不饱和代谢物和4种双不饱和代谢物的形成异常增加，占VPA加所有分析代谢物总和的58-71%(对照组最高15%)，尿中34-61%(对照组最高10%)。VPA的β-氧化途径受到抑制(缺少3-酮-VPA)，而omega-氧化途径的代谢物仍可被检测到(尿5-OH-VPA加上2-丙基戊二酸.apprx)。16%，控制10%以上)。4-烯-VPA(2-丙基-4-戊烯酸)(5~21%)和4，4‘-二烯-VPA(2(2-丙烯)-4-戊烯酸)(4~7%)是正常对照中未检出的异常不饱和代谢物。其他典型的发现是己二酸、琥珀酸和4-辛烯-1，8-二羧酸的高排泄量，表明在脂肪酸氧化中欧米伽氧化的能力增强。
A 7-yr-old boy developed a severe unilateral grand mal seizure at the age of 5 yr (phenobarbitone therapy); 1.5 yr later valproate (2-propylpentanoic acid, VPA) was added to the therapy. After a seizure-free period of 3 mo. the patient died from hepatic failure resmebling Reye syndrome. Several plasma and urine samples from the final stage before and during peritoneal dialysis were analyzed by GC/MS [gas chromatography/mass spectroscopy]. The predominant feature was the abnormally increased formation of both 3 mono- and 4 double unsaturated metabolites of VPA amounting in plasma to 58-71% of the sum of VPA plus all analyzed metabolites (controls maximal 15%) and in urine to 34-61% (controls maximal 10%). The beta-oxidation pathway of VPA was suppressed (lack of 3-keto-VPA), whereas metabolites from the omega-oxidation pathway could still be measured (urinary 5-OH-VPA plus 2-propylglutaric acid .apprx. 16%, controls more than 10%). 4-en-VPA (2-propyl-4-pentenoic acid) (5-21% in plasma) and 4,4''-dien-VPA (2(2-propenyl)-4-pentenoic acid) (4-7%) was found as abnormal unsaturated metabolites not detectable in controls. Additional typical findings were the high excretion of adipic acid, suberic acid and 4-octen-1,8-dicarboxylic acid demonstrating the enhanced capacity of omega-oxidation in fatty acid oxidation.