Bennett Jennifer, Gilkes Christy, Klassen Karin, Kerr Marina, Khan Aneal
Department of Medical Genetics and Pediatrics, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Child Neurol Open. 2020 Oct 22;7:2329048X20967880. doi: 10.1177/2329048X20967880. eCollection 2020 Jan-Dec.
This case report describes 2 siblings with myoclonic epilepsy who had novel mutations in the glutamine synthetase () gene: c.316C>T, p.(Arg106*) and c.42G>C, p.(Lys14Asn). Valproic acid improved seizure control, but was associated with hyperammonemic encephalopathy. Addition of carglumic acid reduced ammonia levels but drug coverage was declined. We therefore designed a protocol to measure the reduction in plasma ammonia in response to carglumic acid therapy. After the first dose of carglumic acid, Patient 1 showed a reduction in plasma ammonia levels within 3 hours, from 114 umol/L to 68 umol/L (reference 12-47 umol/L), and Patient 2 from 108 umol/L to 80 umol/L, which was sustained over a 2 week period. Overall, there was a strong negative correlation between plasma ammonia levels and carglumic acid levels (r = -0.86, = 0.0013), and recurrence of hyperammonemic encephalopathy was not observed while the patients were taking carglumic acid.
本病例报告描述了2名患有肌阵挛性癫痫的兄弟姐妹，他们的谷氨酰胺合成酶（）基因存在新的突变：c.316C>T，p.(Arg106*)和c.42G>C，p.(Lys14Asn)。丙戊酸改善了癫痫控制，但与高氨血症性脑病有关。添加卡谷氨酸降低了氨水平，但药物覆盖范围下降。因此，我们设计了一个方案来测量卡谷氨酸治疗后血浆氨的降低情况。在首次给予卡谷氨酸后，患者1在3小时内血浆氨水平从114 μmol/L降至68 μmol/L（参考值12 - 47 μmol/L），患者2从108 μmol/L降至80 μmol/L，并在2周内持续保持。总体而言，血浆氨水平与卡谷氨酸水平之间存在很强的负相关性（r = -0.86， = 0.0013），并且在患者服用卡谷氨酸期间未观察到高氨血症性脑病复发。
