Podell M, Shelton G D, Nyhan W L, Wagner S O, Genders A, Oglesbee M, Fenner W R
Department of Veterinary Clinical Sciences, Ohio State University, Columbus 43210, USA.
Metab Brain Dis. 1996 Sep;11(3):239-47. doi: 10.1007/BF02237961.
A 12 week old female Labrador retriever dog with signs of progressive diffuse degeneration of the brain and spinal cord was found to have methylmalonic and malonic aciduria. Over a 5 month period, the dog developed neurologic signs compatible with disease of the central nervous system with predominant diffuse cerebral and right lateralizing brainstem deficits. Gross pathological examination of the brain showed that the lateral, third, and fourth ventricles of the brain were markedly enlarged and associated with white and grey matter atrophy. Syringomyelia and hydromyelia of the central canal into the dorsal funiculus of the spinal cord beginning at the level of the cervical intumescence and extending to the lumbar intumescence was also present. Significant biochemical abnormalities include methylmalonic and malonic aciduria, mild lactic and pyruvic aciduria. There was also accumulation of citric acid cycle intermediates including succinic, aconitic, and fumaric acids. Disordered fatty acid oxidation was suggested by increased excretion of adipic, ethylmalonic, suberic and sebacic acids. Neither ketoacidosis nor hyperammonemia were present, and serum cobalamin levels were normal. Overall, this dog demonstrates an inborn error of metabolism resulting in abnormal organic acid accumulation associated with a neurodegenerative disease.
一只12周龄的雌性拉布拉多寻回犬出现脑和脊髓进行性弥漫性变性的症状，被发现患有甲基丙二酸尿症和丙二酸尿症。在5个月的时间里，这只狗出现了与中枢神经系统疾病相符的神经症状，主要表现为弥漫性脑和右侧脑干功能缺损。脑部大体病理检查显示，脑的侧脑室、第三脑室和第四脑室明显扩大，并伴有白质和灰质萎缩。脊髓中央管从颈膨大水平开始向脊髓背侧索延伸至腰膨大处出现空洞症和积水性脊髓空洞症。显著的生化异常包括甲基丙二酸尿症和丙二酸尿症、轻度乳酸尿症和丙酮酸尿症。还存在柠檬酸循环中间产物的积累，包括琥珀酸、乌头酸和富马酸。己二酸、乙基丙二酸、辛二酸和癸二酸排泄增加提示脂肪酸氧化紊乱。既没有酮症酸中毒也没有高氨血症，血清钴胺素水平正常。总体而言，这只狗表现出一种先天性代谢错误，导致与神经退行性疾病相关的异常有机酸积累。
