Plasma α-Ketoglutarate in Urea Cycle Enzymopathies and Its Role as a Harbinger of Hyperammonemic Coma
Plasma α-Ketoglutarate in Urea Cycle Enzymopathies and Its Role as a Harbinger of Hyperammonemic Coma
复制标题
尿素循环酶病中的血浆 α-酮戊二酸及其作为高氨血症昏迷先兆的作用
作者：
M. Batshaw;M. Walser;S. Brusilow
摘要：两例鸟氨酸转氨基甲酰基酶缺乏症婴儿早期高氨血症的代谢观察表明，血浆α-酮戊二酸浓度（[α-KG]）在发展为高氨血症昏迷之前就已低于正常水平。在一个案例中，血浆[NH4+]保持正常，直到40日龄上升到57 μM。然而，在27日龄时，高氨血症发生之前，血浆[α-KG]降至15 μM。直到50日龄出现严重高氨血症后才发生昏迷。第二例患者血浆[α-KG]在血浆铵浓度[NH4+]升高（52 μM）前8天（高氨血症昏迷发生前14天）出现亚正常（14 μM）。在8例尿素循环酶病患者中，[NH4+]与[α-KG]呈极显著（P≤0.01）负线性相关。门脉-全身性脑病患者[NH4+]与[α-KG]之间也存在类似的关系，尽管这些患者的绝对[α-KG]水平正常（23±4 μM），而高氨血症患者（88±25 μM）。推测：尿素循环酶病患者血浆[α-KG]和[NH4]水平呈负线性相关，提示血浆[a-KG]可能预示高氨血症昏迷。然而，肝硬化和门脉系统分流患者的[a-KC]水平不同，意味着与肝性昏迷相比，高氨血症昏迷的病理生理机制不同。
Summary: Metabolic observations during early stages of hyperammonemia in two infants with ornithine transcarbamylase deficiency suggest that plasma α-ketoglutarate concentration ([α-KG]) becomes subnormal before the development of hyperammonemic coma. In one case, plasma [NH4+] remained normal until 40 days of age when it rose to 57 μM. However, this hyperammonemia was preceded by a fall in plasma [α-KG] to 15 μM at 27 days of age. It was only after severe hyperammonemia was established at 50 days of age that coma supervened. In the second case, plasma [α-KG] became subnormal (14 μM) 8 days before the rise in plasma ammonium concentration [NH4+] (52 μM) and 14 days before the onset of hyperammonemic coma. In eight patients with urea cycle enzymopathies, there was a highly significant (P ≤0.01) negative linear correlation between [NH4+] and [α-KG]. In patients with portal-systemic encephalopathy, there was a similar relationship between [NH4+] and [α-KG], although the absolute [α-KG] levels in these patients were normal (23 ± 4 μM) while the patients were hyperammonemic (88 ± 25 μM).Speculation: The inverse linear correlation between [α-KG] and [NH4] levels in patients with urea cycle enzymopathies suggest that plasma [a-KG] may presage hyperammonemic coma. However, the different [a-KC] levels in patients with cirrhosis and portalsystemic shunting imply different pathophysiologic mechanisms for hyperammonemic coma as compared to hepatic coma.