新生儿高氨血症诊断与治疗的专家共识

doi:10.7499/j.issn.1008-8830.2302140

PDF(982 KB)

HTML

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (5) : 437-447. DOI: 10.7499/j.issn.1008-8830.2302140

标准·方案·指南

新生儿高氨血症诊断与治疗的专家共识

中华医学会儿科学分会新生儿学组青年委员会

作者信息 +

Expert consensus on the diagnosis and treatment of neonatal hyperammonemia

The Youth Commission, Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association

Author information +

文章历史 +

摘要

新生儿高氨血症是一种发生于新生儿期的氨代谢紊乱，以血液中氨的异常积累、中枢神经系统功能障碍为主要表现的临床综合征。由于其发病率较低，且临床表现缺乏特异性，易造成误诊、漏诊。为进一步规范新生儿高氨血症的诊断与治疗，中华医学会儿科学分会新生儿学组青年委员会基于国内外临床证据，结合临床实践经验，制定了该专家共识，对新生儿高氨血症的诊断和治疗提出了18条推荐意见。

Abstract

Neonatal hyperammonemia is a disorder of ammonia metabolism that occurs in the neonatal period. It is a clinical syndrome characterized by abnormal accumulation of ammonia in the blood and dysfunction of the central nervous system. Due to its low incidence and lack of specificity in clinical manifestations, it is easy to cause misdiagnosis and missed diagnosis. In order to further standardize the diagnosis and treatment of neonatal hyperammonemia, the Youth Commission, Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association formulated the expert consensus based on clinical evidence in China and overseas and combined with clinical practice experience,and put forward 18 recommendations for the diagnosis and treatment of neonatal hyperaminemia.

导出引用

中华医学会儿科学分会新生儿学组青年委员会. 新生儿高氨血症诊断与治疗的专家共识[J]. 中国当代儿科杂志. 2023, 25(5): 437-447 https://doi.org/10.7499/j.issn.1008-8830.2302140

The Youth Commission, Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association. Expert consensus on the diagnosis and treatment of neonatal hyperammonemia[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(5): 437-447 https://doi.org/10.7499/j.issn.1008-8830.2302140

参考文献

1 Kolchina AN, Yatsyshina EE, Malysheva LV, et al. Diagnostics of inherited metabolic diseases in newborns with the hyperammonemia syndrome at the onset of disease (pilot study)[J]. Sovrem Tekhnologii Med, 2021, 13(1): 59-64. PMID: 34513067. PMCID: PMC8353695. DOI: 10.17691/stm2021.13.1.07.
2 Ribas GS, Lopes FF, Deon M, et al. Hyperammonemia in inherited metabolic diseases[J]. Cell Mol Neurobiol, 2022, 42(8): 2593-2610. PMID: 34665389. DOI: 10.1007/s10571-021-01156-6.
3 Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations[J]. BMJ, 2008, 336(7650): 924-926. PMID: 18436948. PMCID: PMC2335261. DOI: 10.1136/bmj.39489.470347.AD.
4 Raina R, Bedoyan JK, Lichter-Konecki U, et al. Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy[J]. Nat Rev Nephrol, 2020, 16(8): 471-482. PMID: 32269302. PMCID: PMC7366888. DOI: 10.1038/s41581-020-0267-8.
5 Alfadhel M, Mutairi FA, Makhseed N, et al. Guidelines for acute management of hyperammonemia in the Middle East region[J]. Ther Clin Risk Manag, 2016, 12: 479-487.
6 Auron A, Brophy PD. Hyperammonemia in review: pathophysiology, diagnosis, and treatment[J]. Pediatr Nephrol, 2012, 27(2): 207-222. PMID: 21431427. DOI: 10.1007/s00467-011-1838-5.
7 Colombo JP, Peheim E, Kretschmer R, et al. Plasma ammonia concentrations in newborns and children[J]. Clin Chim Acta, 1984, 138(3): 283-291. PMID: 6723064. DOI: 10.1016/0009-8981(84)90135-9.
8 H?berle J. Clinical and biochemical aspects of primary and secondary hyperammonemic disorders[J]. Arch Biochem Biophys, 2013, 536(2): 101-108. PMID: 23628343. DOI: 10.1016/j.abb.2013.04.009.
9 H?berle J. Clinical practice: the management of hyperammonemia[J]. Eur J Pediatr, 2011, 170(1): 21-34. PMID: 21165747. DOI: 10.1007/s00431-010-1369-2.
10 Warrillow S, Fisher C, Bellomo R. Correction and control of hyperammonemia in acute liver failure: the impact of continuous renal replacement timing, intensity, and duration[J]. Crit Care Med, 2020, 48(2): 218-224. PMID: 31939790. DOI: 10.1097/CCM.0000000000004153.
11 Bergmann KR, McCabe J, Smith TR, et al. Late-onset ornithine transcarbamylase deficiency: treatment and outcome of hyperammonemic crisis[J]. Pediatrics, 2014, 133(4): e1072-e1076. PMID: 24616362. DOI: 10.1542/peds.2013-1324.
12 Lee B, Diaz GA, Rhead W, et al. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder[J]. Genet Med, 2015, 17(7): 561-568. PMID: 25503497. PMCID: PMC4465427. DOI: 10.1038/gim.2014.148.
13 Nakamura K, Kido J, Mitsubuchi H, et al. Diagnosis and treatment of urea cycle disorder in Japan[J]. Pediatr Int, 2014, 56(4): 506-509. PMID: 25039902. DOI: 10.1111/ped.12439.
14 Bigot A, Tchan MC, Thoreau B, et al. Liver involvement in urea cycle disorders: a review of the literature[J]. J Inherit Metab Dis, 2017, 40(6): 757-769. PMID: 28900784. DOI: 10.1007/s10545-017-0088-5.
15 Ogier de Baulny H, Schiff M, Dionisi-Vici C. Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder[J]. Mol Genet Metab, 2012, 106(1): 12-17. PMID: 22402328. DOI: 10.1016/j.ymgme.2012.02.010.
16 Ro?enková K, Güemes M, Shah P, et al. The diagnosis and management of hyperinsulinaemic hypoglycaemia[J]. J Clin Res Pediatr Endocrinol, 2015, 7(2): 86-97. PMID: 26316429. PMCID: PMC4563192. DOI: 10.4274/jcrpe.1891.
17 Martinelli D, H?berle J, Rubio V, et al. Understanding pyrroline-5-carboxylate synthetase deficiency: clinical, molecular, functional, and expression studies, structure-based analysis, and novel therapy with arginine[J]. J Inherit Metab Dis, 2012, 35(5): 761-776. PMID: 22170564. DOI: 10.1007/s10545-011-9411-8.
18 Ballard RA, Vinocur B, Reynolds JW, et al. Transient hyperammonemia of the preterm infant[J]. N Engl J Med, 1978, 299(17): 920-925. PMID: 692597. DOI: 10.1056/NEJM197810262991704.
19 王恋, 李娟, 毛健, 等. 极低及超低出生体重儿的预后因素分析[J]. 中国当代儿科杂志, 2014, 16(6): 601-605. PMID: 24927435. DOI: 10.7499/j.issn.1008-8830.2014.06.008.
20 Vergano SA, Crossette JM, Cusick FC, et al. Improving surveillance for hyperammonemia in the newborn[J]. Mol Genet Metab, 2013, 110(1-2): 102-105. PMID: 23746553. PMCID: PMC3755016. DOI: 10.1016/j.ymgme.2013.05.005.
21 Van Geet C, Vandenbossche L, Eggermont E, et al. Possible platelet contribution to pathogenesis of transient neonatal hyperammonaemia syndrome[J]. Lancet, 1991, 337(8733): 73-75. PMID: 1670726. DOI: 10.1016/0140-6736(91)90736-9.
22 Tuchman M, Georgieff MK. Transient hyperammonemia of the newborn: a vascular complication of prematurity?[J]. J Perinatol, 1992, 12(3): 234-236. PMID: 1432279.
23 Ames EG, Powell C, Engen RM, et al. Multisite retrospective review of outcomes in renal replacement therapy for neonates with inborn errors of metabolism[J]. J Pediatr, 2022, 246: 116-122.e1. PMID: 35358588. PMCID: PMC9233075. DOI: 10.1016/j.jpeds.2022.03.043.
24 Westrope C, Morris K, Burford D, et al. Continuous hemofiltration in the control of neonatal hyperammonemia: a 10-year experience[J]. Pediatr Nephrol, 2010, 25(9): 1725-1730. PMID: 20495829. DOI: 10.1007/s00467-010-1549-3.
25 曾健生. 高氨血症相关遗传代谢病危重症[J]. 中国实用儿科杂志, 2015, 30(8): 573-578. DOI: 10.7504/ek2015080604.
26 金润铭, 杨爱德. 小儿高氨血症的诊断和治疗[J]. 中国实用儿科杂志, 2000, 15(2): 75-77. DOI: 10.3969/j.issn.1005-2224.2000.02.005.
27 陆妹. 尿素循环障碍导致的危重症识别及对策[J]. 中国实用儿科杂志, 2021, 36(10): 735-738. DOI: 10.19538/j.ek2021100604.
28 中国医师协会医学遗传医师分会临床生化专业委员会, 中华医学会儿科学分会内分泌遗传代谢学组, 中国妇幼保健协会儿童疾病和保健分会遗传代谢学组, 等. 中国尿素循环障碍诊断治疗和管理指南[J]. 中华儿科杂志, 2022, 60(11): 1118-1126. PMID: 36319144. DOI: 10.3760/cma.j.cn112140-20220412-00319.
29 Paprocka J, Jamroz E. Hyperammonemia in children: on the crossroad of different disorders[J]. Neurologist, 2012, 18(5): 261-265. PMID: 22931730. DOI: 10.1097/NRL.0b013e318266f58a.
30 Matoori S, Leroux JC. Recent advances in the treatment of hyperammonemia[J]. Adv Drug Deliv Rev, 2015, 90: 55-68. PMID: 25895618. DOI: 10.1016/j.addr.2015.04.009.
31 Bachmann C. Mechanisms of hyperammonemia[J]. Clin Chem Lab Med, 2002, 40(7): 653-662. PMID: 12241009. DOI: 10.1515/CCLM.2002.112.
32 Dasarathy S, Mookerjee RP, Rackayova V, et al. Ammonia toxicity: from head to toe?[J]. Metab Brain Dis, 2017, 32(2): 529-538. PMID: 28012068. PMCID: PMC8839071. DOI: 10.1007/s11011-016-9938-3.
33 Broomfield A, Grunewald S. How to use serum ammonia[J]. Arch Dis Child Educ Pract Ed, 2012, 97(2): 72-77; answer to quiz pg 80. PMID: 22101094. DOI: 10.1136/archdischild-2011-300194.
34 Hansen L, Lind-Thomsen A, Joshi HJ, et al. A glycogene mutation map for discovery of diseases of glycosylation[J]. Glycobiology, 2015, 25(2): 211-224. PMID: 25267602. PMCID: PMC4351397. DOI: 10.1093/glycob/cwu104.
35 Tarailo-Graovac M, Shyr C, Ross CJ, et al. Exome sequencing and the management of neurometabolic disorders[J]. N Engl J Med, 2016, 374(23): 2246-2255. PMID: 27276562. PMCID: PMC4983272. DOI: 10.1056/NEJMoa1515792.
36 Taylor RW, Pyle A, Griffin H, et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies[J]. JAMA, 2014, 312(1): 68-77. PMID: 25058219. PMCID: PMC6558267. DOI: 10.1001/jama.2014.7184.
37 H?berle J, Burlina A, Chakrapani A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision[J]. J Inherit Metab Dis, 2019, 42(6): 1192-1230. PMID: 30982989. DOI: 10.1002/jimd.12100.
38 Burton BK. Inborn errors of metabolism in infancy: a guide to diagnosis[J]. Pediatrics, 1998, 102(6): E69. PMID: 9832597. DOI: 10.1542/peds.102.6.e69.
39 Leonard JV, Morris AA. Diagnosis and early management of inborn errors of metabolism presenting around the time of birth[J]. Acta Paediatr, 2006, 95(1): 6-14. PMID: 16373289. DOI: 10.1080/08035250500349413.
40 Batshaw ML, Wachtel RC, Cohen L, et al. Neurologic outcome in premature infants with transient asymptomatic hyperammonemia[J]. J Pediatr, 1986, 108(2): 271-275. PMID: 3511207. DOI: 10.1016/s0022-3476(86)81003-4.
41 Enns GM, Berry SA, Berry GT, et al. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders[J]. N Engl J Med, 2007, 356(22): 2282-2292. PMID: 17538087. DOI: 10.1056/NEJMoa066596.
42 Chakrapani A, Cleary MA, Wraith JE. Detection of inborn errors of metabolism in the newborn[J]. Arch Dis Child Fetal Neonatal Ed, 2001, 84(3): F205-F210. PMID: 11320051. PMCID: PMC1721249. DOI: 10.1136/fn.84.3.f205.
43 Wang HS, Kuo MF, Chou ML, et al. Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy[J]. Arch Dis Child, 2005, 90(5): 512-515. PMID: 15851435. PMCID: PMC1720393. DOI: 10.1136/adc.2003.045963.
44 Nasser M, Javaheri H, Fedorowicz Z, et al. Carnitine supplementation for inborn errors of metabolism[J]. Cochrane Database Syst Rev, 2012, 2012(2): CD006659. PMID: 22336821. PMCID: PMC7390060. DOI: 10.1002/14651858.CD006659.pub3.
45 Batshaw ML, Brusilow S, Waber L, et al. Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion[J]. N Engl J Med, 1982, 306(23): 1387-1392. PMID: 7078580. DOI: 10.1056/NEJM198206103062303.
46 Matoori S, Forster V, Agostoni V, et al. Preclinical evaluation of liposome-supported peritoneal dialysis for the treatment of hyperammonemic crises[J]. J Control Release, 2020, 328: 503-513. PMID: 32860926. DOI: 10.1016/j.jconrel.2020.08.040.
47 Chen YJ, Hung HH, Li CY, et al. A central venous catheter as an alternative peritoneal dialysis tube in an extremely low birth weight infant: a practical life-saving method for medical-resource-limited institutions[J]. J Formos Med Assoc, 2021, 120(10): 1928-1929. PMID: 34247892. DOI: 10.1016/j.jfma.2021.06.021.
48 Le Page AK, Stewart AE, Roehr CC, et al. The use of peritoneal dialysis in phenobarbitone toxicity in a critically unwell neonate[J]. Neonatology, 2018, 113(2): 117-121. PMID: 29169160. DOI: 10.1159/000481879.
49 Wu X, Vega M, Swartz SJ, et al. Milky appearance of peritoneal fluid in a neonate on peritoneal dialysis due to end-stage renal disease: answers[J]. Pediatr Nephrol, 2018, 33(1): 73-76. PMID: 28283762. DOI: 10.1007/s00467-017-3633-4.
50 Celik M, Akdeniz O, Ozgun N. Efficacy of peritoneal dialysis in neonates presenting with hyperammonaemia due to urea cycle defects and organic acidaemia[J]. Nephrology (Carlton), 2019, 24(3): 330-335. PMID: 29356227. DOI: 10.1111/nep.13224.
51 中华医学会儿科学分会新生儿学组. 连续性血液净化治疗新生儿急性肾损伤专家共识[J]. 中华儿科杂志, 2021, 59(4): 264-269. PMID: 33775043. DOI: 10.3760/cma.j.cn112140-20200922-00898.
52 Bellomo R, Baldwin I, Ronco C, et al. ICU-based renal replacement therapy[J]. Crit Care Med, 2021, 49(3): 406-418. PMID: 33555775. DOI: 10.1097/CCM.0000000000004831.
53 See EJ, Bellomo R. How I prescribe continuous renal replacement therapy[J]. Crit Care, 2021, 25(1): 1. PMID: 33388077. PMCID: PMC7777364. DOI: 10.1186/s13054-020-03448-7.
54 周文浩, 陆国平. 连续性血液净化治疗新生儿急性肾损伤专家共识解读[J]. 中华儿科杂志, 2021, 59(4): 270-272. PMID: 33775044. DOI: 10.3760/cma.j.cn112140-20210126-00071.
55 Eisenstein I, Pollack S, Hadash A, et al. Acute hemodialysis therapy in neonates with inborn errors of metabolism[J]. Pediatr Nephrol, 2022, 37(11): 2725-2732. PMID: 35239033. DOI: 10.1007/s00467-022-05507-3.
56 Spinale JM, Laskin BL, Sondheimer N, et al. High-dose continuous renal replacement therapy for neonatal hyperammonemia[J]. Pediatr Nephrol, 2013, 28(6): 983-986. PMID: 23471476. PMCID: PMC3633740. DOI: 10.1007/s00467-013-2441-8.
57 Chan WK, But WM, Law CW. Ammonia detoxification by continuous venovenous haemofiltration in an infant with urea cycle defect[J]. Hong Kong Med J, 2002, 8(3): 207-210. PMID: 12055368.
58 Picca S, Dionisi-Vici C, Bartuli A, et al. Short-term survival of hyperammonemic neonates treated with dialysis[J]. Pediatr Nephrol, 2015, 30(5): 839-847. PMID: 25185886. DOI: 10.1007/s00467-014-2945-x.
59 Lai YC, Huang HP, Tsai IJ, et al. High-volume continuous venovenous hemofiltration as an effective therapy for acute management of inborn errors of metabolism in young children[J]. Blood Purif, 2007, 25(4): 303-308. PMID: 17643056. DOI: 10.1159/000106102.
60 Unsinn C, Das A, Valayannopoulos V, et al. Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001-2013[J]. Orphanet J Rare Dis, 2016, 11(1): 116. PMID: 27538463. PMCID: PMC4991093. DOI: 10.1186/s13023-016-0493-0.
61 Bijarnia-Mahay S, H?berle J, Jalan AB, et al. Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing[J]. Orphanet J Rare Dis, 2018, 13(1): 174. PMID: 30285816. PMCID: PMC6167905. DOI: 10.1186/s13023-018-0908-1.
62 Kido J, Matsumoto S, Ito T, et al. Physical, cognitive, and social status of patients with urea cycle disorders in Japan[J]. Mol Genet Metab Rep, 2021, 27: 100724. PMID: 33614409. PMCID: PMC7876628. DOI: 10.1016/j.ymgmr.2021.100724.
63 Kido J, Matsumoto S, H?berle J, et al. Long-term outcome of urea cycle disorders: report from a nationwide study in Japan[J]. J Inherit Metab Dis, 2021, 44(4): 826-837. PMID: 33840128. DOI: 10.1002/jimd.12384.
64 Kido J, Matsumoto S, H?berle J, et al. Role of liver transplantation in urea cycle disorders: report from a nationwide study in Japan[J]. J Inherit Metab Dis, 2021, 44(6): 1311-1322. PMID: 34232532. DOI: 10.1002/jimd.12415.
65 McBride KL, Miller G, Carter S, et al. Developmental outcomes with early orthotopic liver transplantation for infants with neonatal-onset urea cycle defects and a female patient with late-onset ornithine transcarbamylase deficiency[J]. Pediatrics, 2004, 114(4): e523-e526. PMID: 15466081. DOI: 10.1542/peds.2004-0198.