近日，美国FDA内分泌及代谢药物咨询委员会以12票赞成，0票反对的投票结果肯定了意大利Recordati公司血液疾病治疗药Carbaglu，该药用于治疗高氨血症——罕见的常染色体遗传性疾病，可导致N-乙酰谷氨酸合成酶（NAGS）缺乏。而NAGS的缺乏会导致患者体内血氨水平升高，进而会永久性损害其中枢神经系统，具有长期性和致命性的特点。

FDA官员曾就该药的实验设计表示担忧，但同时又表示所有受试患者用药之后未发现严重的安全性问题。总体而言，FDA仍认为由于Carbaglu相关的实验数据在数量和质量上都存在严重不足，因此还不能对药物的疗效下定论。

但内分泌及代谢药物咨询委员并未受到上述观点的影响，他们认为药物相关的临床实验数据可有力论证其疗效，特别是证实该药可以针对治疗血氨水平。相关专业人士表示，这种产品疗效较为显著，为那些患有先天性NAGS缺乏症的儿童带来了希望。

Recordati公司罕见病药事业部欧洲分部也表示，已“充分证实”Carbaglu的疗效。目前NAGS缺乏症新生儿发病率大约为1/30000。Carbaglu的安全性也已得到认可，该公司未被要求就此展开后续工作，但FDA建议应建立相关的监测系统。

N-carbamylglutamate
N-carbamylglutamate can potentially improve hyperammonemia in patients with propionic and methylmalonic acidemia

N-acetylglutamate (NAG) is a chemical produced in the liver that is essential for normal function of the urea cycle; without it, the cycle does not do its job of detoxifying ammonia.  Patients who are deficient in NAG in the liver develop hyperammonemia. There are several causes for NAG deficiency. The most obvious is a genetic defect in N-acetylglutamate synthase (NAGS), the enzyme that produces NAG.  Other causes involve secondary NAG deficiency due to interference with its production by NAGS.  The most known cause for secondary NAG deficiency is propionic acidemia (PA) where the accumulation of propionyl-CoA in liver mitochondria interferes with NAG production.  Methylmalonic acidemia (MMA) presumably manifests the same problem.  Similarly, patients treated with valproic acid may also develop low liver NAG due to interference with NAG production by valproic acid metabolites.  All latter conditions are associated with hyperammonemia presumably due to NAG deficiency.  Since we have recently shown that the drug Carbaglu® (N-carbamylglutamate) restores to normal urea cycle functions and eliminates the hyperammonemia in patients with NAGS deficiency, we further hypothesize that patients with PA and MMA who have hyperammonemia may also benefit from this drug.  In order to investigate this hypothesis, we have launched a study in patients with severe PA and MMA (those who presented with neonatal hyperammonemia).  The study is open to patients with severe PA or MMA who are 5 years and older and consists of oral administration of a stable isotope [13C]sodium acetate before, and following 3 days of Carbaglu treatment, comparing the amount of [13C] that ends up in urea as an indication of urea production rate.  One patient with PA who was studied showed a marked increase of urea production on Carbaglu as well as decrease in glutamine and glycine levels.  If this finding can be reproduced in additional patients with PA or MMA, it will suggest that Carbaglu could effectively treat hyperammonemia episodes in patients with the most common organic acidemias. Although hyperammonemia is only one of the several mechanisms of metabolic derangement in PA or MMA, alleviation of hyperammonemia could facilitate the management of these patients.

高氨血症　　肝功能严重损伤时尿素合成障碍导致血氨浓度升高。
高氨血症的治疗
[1]应尽快从体内排出血氨，同时给予足够的热量及必需氨基酸以减少体内蛋白质得分解。
[2]静脉输入足量的液体及电解质，为补充热量可加入葡萄糖及胰岛素，静脉输入脂肪每天1g/kg。
[3]静脉输入苯甲酸钠和苯乙酸钠。由于肾脏对氨的清除能力低下，因此有必要使氨形成一种易于被肾脏清除的化合物，苯甲酸钠能与内源性的甘氨酸结合形成马尿酸，后者的肾脏清出率甚高，苯乙酸钠与谷氨酸结合形成苯乙酸谷氨酸而易与从尿中排出。急救时可用苯甲酸钠及苯乙酸钠各250mg/kg加入10%葡萄糖，液体量按20ml/kg，于2小时内静脉输入，以后每日给苯甲酸钠和苯乙酸钠各250~500mg/kg静脉输入。
[4]盐酸精氨酸 除因精氨酸酶缺陷所致的高氨血症外，其余的病例均可采用精氨酸治疗。精氨酸既可促进氨的排出，同时有补充体内必须的氨基酸。对新生儿首次发生的高氨血症而病因未明时，在急救时可给予精氨酸。对于继发于有机酸血症的高氨血症，精氨酸无治疗作用。苯甲酸、苯乙酸、精氨酸同时应用可取的最佳的疗效，在首次用药后应持续静点直至急性危重症好转。
[5]血液透析或腹膜透析 在上诉方法治疗数小时时血氨水平无明显下降，应采用血液透析或腹膜透析疗法。腹膜透析数小时后血氨水平可明显下降，大多数经48小时透析血氨水平可恢复正常。
[6]新霉素及乳果糖 为了减少肠道细菌产氨，应尽早鼻饲或灌肠给予新霉素或乳果糖，患儿经急救措施神经危重症状得以缓解，但可能还需数日神志才能完全恢复清醒。
[7]饮食治疗 患者应限制蛋白质的摄入，每天供给蛋白质1~2g/kg。
[8]补充肉碱 在以上治疗中应补充肉碱，因苯甲酸和苯乙酸都可引起体内肉碱缺乏。
[9]此外该类患儿惊厥不能应用丙戊酸，因此药可诱发高氨血症。