卡尼汀继发性缺乏.pptVIP

OCTN: 有机阳离子转运器,细胞膜上的转运蛋白，负责转运血浆中的卡尼汀进入细胞质 * * In 1982, I diagnosed my first patient with Methylmalonic acidria due to a complete block in the enzyme converting methylmalonyl CoA to Succinyl CoA, the B12 dependent methylmalonyl CoA mutase. This patient presented in the newborn period with metabolic acidosis, hypoglycemia and lethargy. 1982年,我诊断了第一个甲基丙二酸尿症的患者，由于完全阻断了将甲基丙二酰辅酶A转化为琥珀酰辅酶A的酶,即依赖B12的甲基丙二酸辅酶A变位酶。 这个病人在新生儿期出现代谢性酸中毒、低血糖和嗜睡。 SIGN-2 Pediatric slides * * MMA results in an increased excretion of propionyl carnitine in the urine which was not well understood in 1982. MMA was known to be a severe organic aciduria with most patients dying by age 5. Carnitine treatment was not described for this disorder at the time he was diagnosed. SIGN-2 Pediatric slides * * He was treated initially with a diet deficient in the amino acid precursors of MMA and did well as evidenced in the first picture I showed at age 4 months. However, over the next 5 months he developed severe failure to thrive, chronic infections, muscle weakness and required multiple hospitalizations. At this time, I questioned why he had previously thrived on his diet and now was not thriving. I turned to my colleagues and a report of carnitine deficiency in isovaleric acidemia was brought to my attention. I found a laboratory to measure his blood carnitine and the results came back showing 他最初是用缺乏甲基丙二酸尿症（MMA）氨基酸前体的饮食治疗，最初效果不错,这体现在我出示的第一个图，这时是4个月。 接下来的5个月，他患上严重的成长障碍、慢性感染、肌肉无力和所需的多个住院，这时我怀疑为什么开始可以生长，现在反而不能生长了，我向我的同时求助，异戊酸血症的卡尼汀缺乏的报道引起了我的注意，找了实验室来测定他的血液中的卡尼汀，结果回来显示、、、、 甲基丙二酸尿症，又称甲基丙二酸血症，英文名字：methylmalonic academia,MMA属常染色体隐性遗传。临床主要表现为早婴期起病，严重的间歇性酮酸中毒，血和尿中甲基丙二酸增多。根据甲基丙二酸辅酶A变位酶缺陷分为完全缺失Mut0和部分却失Mut1型，其中最严重的是Mut0型。 SIGN-2 Pediatric slides * * A very low free carnitine level of 7.9 micromoles/liter in blood and 7.5 micromoles/liter in urine. Dr. Austin Shug, a pioneer in carnitine metabolism, called to alert me about these levels stating that he had only seen such low values in “cadavers” up to that point.