perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2020-65-6-98-107perinatology-1297Research ArticleОБМЕН ОПЫТОМSHARING EXPERIENCESГипераммониемия в практике неонатологаHyperammonemia in Neonatologist Practicehttps://orcid.org/0000-0001-6662-851XДегтяреваА. В.DegtyarevaA. V.

Дегтярева Анна Владимировна – д.м.н., проф., зав. отделом педиатрии Института неонатологии и педиатрии; проф. кафедры неонатологии Института здоровья детей 

117997 Москва, ул. Академика Опарина, д. 4 

Moscow

annadim@yahoo.comhttps://orcid.org/0000-0002-4298-121XСоколоваЕ. В.SokolovaE. V.

Соколова Екатерина Владимировна – врач–анестезиолог-реаниматолог отделения хирургии новорожденных Института неонатологии и педиатрии 

117997 Москва, ул. Академика Опарина, д. 4 

Moscow

https://orcid.org/0000-0002-5020-1180ЗахароваЕ. Ю.ZakharovaE. Yu.

Захарова Екатерина Юрьевна – д.м.н. зав. лабораторией наследственных болезней обмена веществ

115478 Москва, ул. Москворечье, д. 1

Moscow city

https://orcid.org/0000-0002-4515-6389ИсаеваМ. Х.IsaevaM. Kh.

Исаева Медан Хасановна – асп.

117997 Москва, ул. Академика Опарина, д. 4

Moscow

https://orcid.org/0000-0002-4047-6201ВысокихМ. Ю.VysokikhM. Yu.

Высоких Михаил Юрьевич – к.б.н., зав. лабораторией митохондриальной медицины 

117997 Москва, ул. Академика Опарина, д. 4 

Moscow

ИванецТ. Ю.IvanetsT. Yu.

Иванец Татьяна Юрьевна – д.м.н., зав. клинико-диагностической лабораторией

117997 Москва, ул. Академика Опарина, д. 4 

Moscow

https://orcid.org/0000-0001-8975-2425ДегтяревД. Н.DegtyarevD. N.

Дегтярев Дмитрий Николаевич – д.м.н., проф., зам. директора по научной работе; зав. кафедрой неонатологии Института здоровья детей 

117997 Москва, ул. Академика Опарина, д. 4 

Moscow

ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. В.И. Кулакова» Минздрава России; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РФ (Сеченовский университет)РоссияNational Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. В.И. Кулакова» Минздрава РоссииРоссияNational Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. KulakovRussian FederationФГБНУ «Медико-генетический научный центр им. академика Н.П. Бочкова»РоссияN.P. Bochkov Research Centre for Medical GeneticsRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияN.I. Pirogov Russian National Research Medical UniversityRussian FederationФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. В.И. Кулакова» Минздрава России; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РФРоссияNational Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation20202101202165698107Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20212021Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/1297

Неонатальная гипераммониемия – патологическое состояние, возникающее в периоде новорожденности, характеризующееся повышенным содержанием свободных ионов аммония в крови и приводящее к тяжелым неврологическим расстройствам. Гипераммониемия у новорожденных служит одним из проявлений широкого круга как первичных (наследственно обусловленных), так и вторичных нарушений обмена веществ. В зависимости от конкретной причины гипераммонемия в периоде новорожденности может иметь стойкий или транзиторный характер. Клинические признаки данного состояния, как правило, неспецифичны. Отмечаются неврологические нарушения различной степени выраженности: синдром возбуждения или угнетения ЦНС, эпизоды апноэ, диффузная мышечная гипотония, судорожный синдром и кома. Гипераммониемия может сопровождаться респираторными расстройствами и приводить к развитию полиорганной недостаточности, что напоминает клинический симптомокомплекс сепсиса. Тяжесть поражения головного мозга коррелирует со степенью повышения концентрации аммиака и продолжительностью гипераммониемии. Ранняя диагностика гипераммонемии позволяет сохранить жизнь ребенка, предупредить тяжелые неврологические последствия и снизить риск инвалидизации. Кроме того, выявление наследственных болезней обмена, сопровождающихся гипераммониемией, определяет необходимость проведения медико-генетического консультирования семьи, а также пренатальной и преимплантационной диагностики.

The neonatal hyperammonemia is the pathological condition that occurs during the neonatal period; it is characterized by the increased content of the free ammonium ions in the blood, and it causes the severe neurological disorders. The hyperammonemia in the newborns is one of the manifestations of a wide range of both primary (hereditary) and secondary metabolic disorders. Depending on the specific cause, the hyperammonemia in the neonatal period can be of the persistent or transient nature. As a rule, the clinical signs of this condition are nonspecific. The neurological disorders of the varying severity are noted, as follows: CNS (central nervous system) excitement or depression syndrome, episodes of apnea, diffuse muscular hypotonia, convulsive disorder and coma. The hyperammonemia can be accompanied by the respiratory disorders, and it can cause the development of the multiple organ failure that resembles the clinical symptom complex of the sepsis. The severity of brain damage correlates with the degree of increase in the ammonia concentration and hyperammonemia duration. Early diagnosis of the hyperammonemia allows to save the child’s life, to prevent the severe neurological consequences and to reduce the risk of disability. Moreover, the identification of the hereditary metabolic diseases accompanied by the hyperammonemia determines the necessity to carry out the genetic counselling of the family, as well as the prenatal and preimplantation genetic diagnosis.

детинеонатальная гипераммониемиянаследственные болезни обмена веществредкие (орфанные) заболеванияпоражение ЦНСсудороги неясной этиологиисептикоподобный симптомокомплексchildrenneonatal hyperammonemiahereditary metabolic diseasesrare (orphan) diseasesCNS damageconvulsions of unknown etiologysepsis-like symptom complexReferencesGropman A.L., Summar M., Leonard J.V. Neurological implications of urea cycle disorders. J Inherit Metab Dis 2007; 30: 865–879. DOI: 10.1007/s10545-007-0709-5Gropman A.L., Summar M., Leonard J.V. Neurological implications of urea cycle disorders. J Inherit Metab Dis 2007; 30: 865–879. DOI: 10.1007/s10545-007-0709-5Joseph M., Hageman J.R. Neonatal Transport: A 3-DayOld Neonate with Hypothermia, Respiratory Distress, Lethargy and Poor Feeding. J Perinatol 2002; 22: 506–509. DOI: 10.1038/sj.jp.7210755Joseph M., Hageman J.R. Neonatal Transport: A 3-DayOld Neonate with Hypothermia, Respiratory Distress, Lethargy and Poor Feeding. J Perinatol 2002; 22: 506–509. DOI: 10.1038/sj.jp.7210755Leonard J.V., Morris A.A. Urea Cycle Disorders. Semin Neonatol 2002; 7: 27–35. DOI: 10.1053/siny.2001.0085Leonard J.V., Morris A.A. Urea Cycle Disorders. Semin Neonatol 2002; 7: 27–35. DOI: 10.1053/siny.2001.0085Brar G., Thomas R., Bawle E. Transient Hyperammonemia in Preterm Infants With Hypoxia. Pediatr Res 2004; 56: 671. DOI: 10.1203/00006450-200410000-00052Brar G., Thomas R., Bawle E. Transient Hyperammonemia in Preterm Infants With Hypoxia. Pediatr Res 2004; 56: 671. DOI: 10.1203/00006450-200410000-00052Enns G.M. Inborn Errors of Metabolism Masquerading as Hypoxic-Ischemic Encephalopathy. Neo Rev 2005; 6(12): 549–558. DOI: 10.1542/neo.6-12-e549Enns G.M. Inborn Errors of Metabolism Masquerading as Hypoxic-Ischemic Encephalopathy. Neo Rev 2005; 6(12): 549–558. DOI: 10.1542/neo.6-12-e549Haeberle J., Boddaert N., Burlina A., Chakrapani A., Dixon M., Huemer M. et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 2012; 7: 32. DOI: 10.1186/1750-1172-7-32Haeberle J., Boddaert N., Burlina A., Chakrapani A., Dixon M., Huemer M. et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 2012; 7: 32. DOI: 10.1186/1750-1172-7-32Биохимия. Под ред. Е.С. Северина. М.: ГЭОТАР-мед, 2015; 768. [Biochemistry. E.S. Severin (ed.). Moscow: GEOTAR-med, 2015; 768. (in Russ.)]Биохимия. Под ред. Е.С. Северина. М.: ГЭОТАР-мед, 2015; 768. [Biochemistry. E.S. Severin (ed.). Moscow: GEOTAR-med, 2015; 768. (in Russ.)]Dasarathy S., Mookerjee R.P., Rackayova V., Rangroo Thrane V., Vairappan B., Ott P., Rose C.F. Ammonia toxicity: from head to toe? Metab Brain Dis 2017; 32(2): 529–538. DOI: 10.1007/s11011-016-9938-3Dasarathy S., Mookerjee R.P., Rackayova V., Rangroo Thrane V., Vairappan B., Ott P., Rose C.F. Ammonia toxicity: from head to toe? Metab Brain Dis 2017; 32(2): 529–538. DOI: 10.1007/s11011-016-9938-3Wesson D.E., Buysse J.M., Bushinsky D.A. Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease. J Am Soc Nephrol 2020; 31(3): 469–482. DOI: 10.1681/ASN.2019070677Wesson D.E., Buysse J.M., Bushinsky D.A. Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease. J Am Soc Nephrol 2020; 31(3): 469–482. DOI: 10.1681/ASN.2019070677Cauli O., Rodrigo R., Piedrafita B., Boix J., Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatol 2007; 46: 514–519. DOI: 10.1002/hep.21734Cauli O., Rodrigo R., Piedrafita B., Boix J., Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatol 2007; 46: 514–519. DOI: 10.1002/hep.21734Ortiz-Pujols S., Jones S.W., Short K.A., Morrell M.R., Bermudez C.A., Tilley S.L., Cairns B.A. Management and sequelae of a 41-year-old Jehovah’s witness with severe anhydrous ammonia inhalation injury. J Burn Care Res 2014; 35: e180– e183. DOI: 10.1097/BCR.0b013e318299d4d7Ortiz-Pujols S., Jones S.W., Short K.A., Morrell M.R., Bermudez C.A., Tilley S.L., Cairns B.A. Management and sequelae of a 41-year-old Jehovah’s witness with severe anhydrous ammonia inhalation injury. J Burn Care Res 2014; 35: e180– e183. DOI: 10.1097/BCR.0b013e318299d4d7Jia B., Yu Z-J., Duan Z-F., Lü X-Q., Li J-J., Liu X-R. et al. Hyperammonaemia induces hepatic injury with alteration of gene expression profiles. Liver Int 2014; 34: 748–758. DOI: 10.1111/liv.12365Jia B., Yu Z-J., Duan Z-F., Lü X-Q., Li J-J., Liu X-R. et al. Hyperammonaemia induces hepatic injury with alteration of gene expression profiles. Liver Int 2014; 34: 748–758. DOI: 10.1111/liv.12365Qiu J., Tsien C., Thapalaya S., Narayanan A., Weihl C.C., Ching J.K. et al. Hyperammonemia- mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 2012; 303: E983–E993. DOI: 10.1152/ajpendo.00183.2012Qiu J., Tsien C., Thapalaya S., Narayanan A., Weihl C.C., Ching J.K. et al. Hyperammonemia- mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 2012; 303: E983–E993. DOI: 10.1152/ajpendo.00183.2012Duffy T., Plum F. Seizures and comatose states. In: Basic Neurochemistry. G.J. Siegel, R.W. Albers, R. Katzman (eds). Boston: Little Brown, 1981; 857.Duffy T., Plum F. Seizures and comatose states. In: Basic Neurochemistry. G.J. Siegel, R.W. Albers, R. Katzman (eds). Boston: Little Brown, 1981; 857.Hindfelt B., Siesjo B.K. Cerebral effects of acute ammonia intoxication. II. The effect upon energy metabolism, Scand J Clin Lab Invest 1971; 28: 365–374. DOI: 10.3109/00365517109095711Hindfelt B., Siesjo B.K. Cerebral effects of acute ammonia intoxication. II. The effect upon energy metabolism, Scand J Clin Lab Invest 1971; 28: 365–374. DOI: 10.3109/00365517109095711Barkovich A.J. Pediatric Neuroimaging. 4th Еd, Lippincott Williams & Wilkins: Philadelphia, 2005; 206.Barkovich A.J. Pediatric Neuroimaging. 4th Еd, Lippincott Williams & Wilkins: Philadelphia, 2005; 206.Häberle J. Clinical and biochemical aspects of primary and secondary hyperammonemic disorders. Arch Biochem Bioph 2013; 536(2): 101–108. DOI: 10.1016/j.abb.2013.04.009Häberle J. Clinical and biochemical aspects of primary and secondary hyperammonemic disorders. Arch Biochem Bioph 2013; 536(2): 101–108. DOI: 10.1016/j.abb.2013.04.009Robinson M.B., Batshaw M.L. Neurotransmitter alterations in congenital hyperammonemia, Ment Retard Dev Disabil Res Rev 1995; 1: 201–207.Robinson M.B., Batshaw M.L. Neurotransmitter alterations in congenital hyperammonemia, Ment Retard Dev Disabil Res Rev 1995; 1: 201–207.Butterworth R.F. Effects of hyperammonaemia on brain function. J Inherit Metab Dis 1998; 21: 6–20. DOI: 10.1023/a:1005393104494Butterworth R.F. Effects of hyperammonaemia on brain function. J Inherit Metab Dis 1998; 21: 6–20. DOI: 10.1023/a:1005393104494Marcaida G., Felipo V., Hermenegildo C., Minana M.D., Grisolía S. Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors, FEBS Lett 1992; 296: 67–68. DOI: 10.1016/0014-5793 (92) 80404-5Marcaida G., Felipo V., Hermenegildo C., Minana M.D., Grisolía S. Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors, FEBS Lett 1992; 296: 67–68. DOI: 10.1016/0014-5793 (92) 80404-5Monfort P., Kosenko E., Erceg S., Canales J-J., Felipo V. Molecular mechanism of acute ammonia toxicity: role of NMDA receptors. Neurochem Internat 2002; 41(2–3): 95–102. DOI: 10.1016/s0197-0186(02)00029-3Monfort P., Kosenko E., Erceg S., Canales J-J., Felipo V. Molecular mechanism of acute ammonia toxicity: role of NMDA receptors. Neurochem Internat 2002; 41(2–3): 95–102. DOI: 10.1016/s0197-0186(02)00029-3Summar M.L., Koelker S., Freedenberg D., Le Mons C., Häberle J., Lee H.S., Kirmse B. The incidence of urea cycle disorders. Mol Genet Metab 2013; 110: 179–810. DOI: 10.1016/j.ymgme.2013.07.008Summar M.L., Koelker S., Freedenberg D., Le Mons C., Häberle J., Lee H.S., Kirmse B. The incidence of urea cycle disorders. Mol Genet Metab 2013; 110: 179–810. DOI: 10.1016/j.ymgme.2013.07.008Guglielmo R.D., Gallo G., Scolamiero E., Salvatore F., Ruoppolo M. ‘‘Classical organic acidurias’’: diagnosis and pathogenesis. Clin Exp Med 2017; 17(3): 305–323. DOI: 10.1007/s10238-016-0435-0Guglielmo R.D., Gallo G., Scolamiero E., Salvatore F., Ruoppolo M. ‘‘Classical organic acidurias’’: diagnosis and pathogenesis. Clin Exp Med 2017; 17(3): 305–323. DOI: 10.1007/s10238-016-0435-0Sanderson S., Green A., Preece M.A., Burton H. The incidence of inherited metabolic disorders in the west midlands UK. Arch Dis Child 2006; 91(11): 869–899. DOI: 10.1136/adc.2005.091637Sanderson S., Green A., Preece M.A., Burton H. The incidence of inherited metabolic disorders in the west midlands UK. Arch Dis Child 2006; 91(11): 869–899. DOI: 10.1136/adc.2005.091637Дегтярева А.В., Киртбая А.Р., Соколова Е.В., Балашова Е.Н., Ионов О.В., Высоких М.Ю. и др. Неонатальная гипераммониемия – транзиторное состояние или маркер наследственных болезней обмена веществ? Неонатология: новости, мнения, обучение 2018; 7(1): 96–102. [Degtyareva A.V., Kirtbaya A.R., Sokolova E.V., Balashova E.N., Ionov O.V., Vysokikh M.Yu. et al. Neonatal hyperammonemia transient condition or marker of inborn errors of metabolism? Neonatologiya: novosti, mneniya, obuchenie 2018; 7(1): 96–102. DOI: 10.24411/2308-2402-2018-00013]Дегтярева А.В., Киртбая А.Р., Соколова Е.В., Балашова Е.Н., Ионов О.В., Высоких М.Ю. и др. Неонатальная гипераммониемия – транзиторное состояние или маркер наследственных болезней обмена веществ? Неонатология: новости, мнения, обучение 2018; 7(1): 96–102. [Degtyareva A.V., Kirtbaya A.R., Sokolova E.V., Balashova E.N., Ionov O.V., Vysokikh M.Yu. et al. Neonatal hyperammonemia transient condition or marker of inborn errors of metabolism? Neonatologiya: novosti, mneniya, obuchenie 2018; 7(1): 96–102. DOI: 10.24411/2308-2402-2018-00013]Bachmann C., Häberle J., Leonard J.V. Pathophysiology and Management of Hyperammonemia. SPS Publications, Heilbronn, 2006; 157–173.Bachmann C., Häberle J., Leonard J.V. Pathophysiology and Management of Hyperammonemia. SPS Publications, Heilbronn, 2006; 157–173.Hoover W., Ackerman V., Schamberger M., Kumar M., Marshalleck F., Hoyer M. The congenital porto‐caval fistula: A unique presentation and novel intervention. Pediatr Pulmonol 2008; 43: 196–199. DOI: 10.1002/ppul.20727Hoover W., Ackerman V., Schamberger M., Kumar M., Marshalleck F., Hoyer M. The congenital porto‐caval fistula: A unique presentation and novel intervention. Pediatr Pulmonol 2008; 43: 196–199. DOI: 10.1002/ppul.20727Taguchi T., Iwamura S., Mizobuchi M., Terada Y., Gastrointest J. Hepatic arteriovenous malformation with hyperammonemia in Rendu-Osler-Weber syndrome. Liver Dis 2011; 20: 330–331.Taguchi T., Iwamura S., Mizobuchi M., Terada Y., Gastrointest J. Hepatic arteriovenous malformation with hyperammonemia in Rendu-Osler-Weber syndrome. Liver Dis 2011; 20: 330–331.Laube G.F., Superti-Furga A., Losa M., Buttiker V., Berger C., Neuhaus T.J. Hyperammonaemic encephalopathy in a 13-year-old boy. Eur J Pediatr 2002; 161: 163–164. DOI: 10.1007/s00431-001-0887-3Laube G.F., Superti-Furga A., Losa M., Buttiker V., Berger C., Neuhaus T.J. Hyperammonaemic encephalopathy in a 13-year-old boy. Eur J Pediatr 2002; 161: 163–164. DOI: 10.1007/s00431-001-0887-3Cheang H.K., Rangecroft L., Plant N.D., Morris A.A. Hyperammonaemia due to Klebsiella infection in a neuropathic bladder. Pediatr Nephrol 1998; 12: 658–659. DOI: 10.1007/s004670050523Cheang H.K., Rangecroft L., Plant N.D., Morris A.A. Hyperammonaemia due to Klebsiella infection in a neuropathic bladder. Pediatr Nephrol 1998; 12: 658–659. DOI: 10.1007/s004670050523McEwan P., Simpson D., Kirk J.M., Barr D.G., McKenzie K.J. Short Report: Hyperammonaemia in Critically Ill Septic Infants. Arch Dis Child 2001; 84: 512–513. DOI: 10.1136/adc.84.6.512McEwan P., Simpson D., Kirk J.M., Barr D.G., McKenzie K.J. Short Report: Hyperammonaemia in Critically Ill Septic Infants. Arch Dis Child 2001; 84: 512–513. DOI: 10.1136/adc.84.6.512Star K., Edwards I R., Choonara I. Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. PLOS One 2014; 9(10): e108970. DOI: 10.1371/journal.pone.0108970Star K., Edwards I R., Choonara I. Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. PLOS One 2014; 9(10): e108970. DOI: 10.1371/journal.pone.0108970Fernández Colomer B., Rekarte García S., García López J.E., Pérez González C., Montes Granda M., Coto Cotallo G.D. Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid. An Pediatr (Barc) 2014; 81(4): 251–255. DOI: 10.1016/j.anpedi.2013.09.015Fernández Colomer B., Rekarte García S., García López J.E., Pérez González C., Montes Granda M., Coto Cotallo G.D. Valproate-induced hyperammonaemic encephalopathy in a neonate: Treatment with carglumic acid. An Pediatr (Barc) 2014; 81(4): 251–255. DOI: 10.1016/j.anpedi.2013.09.015Silva M.F., Aires C.C., Luis P.B., Ruiter J.P., L I.J., Duran M. et al. Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review. J Inherit Metab Dis 2008; 31: 205–216. DOI: 10.1007/s10545-008-0841-xSilva M.F., Aires C.C., Luis P.B., Ruiter J.P., L I.J., Duran M. et al. Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: A review. J Inherit Metab Dis 2008; 31: 205–216. DOI: 10.1007/s10545-008-0841-xLewis C., Deshpande A., Tesar G.E., Dale R. Valproate-induced Hyperammonemic Encephalopathy: A Brief Review. Curr Med Res Opin 2012; 28: 1039–1042. DOI: 10.1185/03007995.2012.694362Lewis C., Deshpande A., Tesar G.E., Dale R. Valproate-induced Hyperammonemic Encephalopathy: A Brief Review. Curr Med Res Opin 2012; 28: 1039–1042. DOI: 10.1185/03007995.2012.694362Ballard R.A., Vinocur B., Reynolds J.W., Wennberg R.P., Merritt A., Sweetman L., Nyhan W.L. Transient hyperammonemia of the preterm infant. N Engl J Med 1978; 299: 920–925. DOI: 10.1056/NEJM197810262991704Ballard R.A., Vinocur B., Reynolds J.W., Wennberg R.P., Merritt A., Sweetman L., Nyhan W.L. Transient hyperammonemia of the preterm infant. N Engl J Med 1978; 299: 920–925. DOI: 10.1056/NEJM197810262991704Chung M.Y., Chen C.C., Huang L.T., Ko T.Y., Lin Y.J. Transient hyperammonemia in a neonate. Acta Pediatr Taiwan 2005; 46(2): 94–96.Chung M.Y., Chen C.C., Huang L.T., Ko T.Y., Lin Y.J. Transient hyperammonemia in a neonate. Acta Pediatr Taiwan 2005; 46(2): 94–96.Golubnitschaja O., Yeghiazaryan K., Cebioglu M., Morelli M., Marschitz M.H. Birth asphyxia as the major complication in newborns: moving towards improved individual outcomes by prediction, targeted prevention and tailored medical care. EPMA J 2011; 2: 197–210. DOI: 10.1007/s13167-011-0087-9Golubnitschaja O., Yeghiazaryan K., Cebioglu M., Morelli M., Marschitz M.H. Birth asphyxia as the major complication in newborns: moving towards improved individual outcomes by prediction, targeted prevention and tailored medical care. EPMA J 2011; 2: 197–210. DOI: 10.1007/s13167-011-0087-9Swaiman K.F., Ashwal S., Ferrio D.M., Schor N.F. (eds). Swaiman’s Pediatric Neurology principle and practice. 5th ed. Philadelphia: Elsevier/Saunders, 2012; 362.Swaiman K.F., Ashwal S., Ferrio D.M., Schor N.F. (eds). Swaiman’s Pediatric Neurology principle and practice. 5th ed. Philadelphia: Elsevier/Saunders, 2012; 362.Goldberg R.N., Cabal L.A., Sinatra F.R., Plajstek C.E., Hodgman J.E. Hyperammonemia associated with perinatal asphyxia. Pediatrics 1979; 64: 336–341.Goldberg R.N., Cabal L.A., Sinatra F.R., Plajstek C.E., Hodgman J.E. Hyperammonemia associated with perinatal asphyxia. Pediatrics 1979; 64: 336–341.Unsinn C., Das A., Valayannopoulos V., Thimm E., Beblo S., Burlina A. et al. Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013. Orphanet J Rare Dis. 2016; 11(1): 116. DOI: 10.1186/s13023-016-0493-0Unsinn C., Das A., Valayannopoulos V., Thimm E., Beblo S., Burlina A. et al. Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001–2013. Orphanet J Rare Dis. 2016; 11(1): 116. DOI: 10.1186/s13023-016-0493-0Mayatepek E. Inborn Errors of Metabolism – Early Detection, Key Symptoms and Therapeutic Options. 2nd ed. Bremen, Germany: UNI-MED Science, 2017; 109.Mayatepek E. Inborn Errors of Metabolism – Early Detection, Key Symptoms and Therapeutic Options. 2nd ed. Bremen, Germany: UNI-MED Science, 2017; 109.Fabre A., Baumstarck K., Cano A., Loundou A., Berbis J., Chabrol B., Auquier P. Assessment of quality of life of the children and parents affected by inborn errors of metabolism with restricted diet: preliminary results of a cross-sectional study. Health Qual Life Outcomes 2013; 11: 158. DOI: 10.1186/1477-7525-11-158Fabre A., Baumstarck K., Cano A., Loundou A., Berbis J., Chabrol B., Auquier P. Assessment of quality of life of the children and parents affected by inborn errors of metabolism with restricted diet: preliminary results of a cross-sectional study. Health Qual Life Outcomes 2013; 11: 158. DOI: 10.1186/1477-7525-11-158Tietz clinical guide to laboratory tests. A.H.B. Wu (ed.). 4th edit. Philadelphia: WB Saunders/Elsevier, 2006; 1856.Tietz clinical guide to laboratory tests. A.H.B. Wu (ed.). 4th edit. Philadelphia: WB Saunders/Elsevier, 2006; 1856.Shennar H.K., Al-Asmar D., Kaddoura A., Al-Fahoum S. Diagnosis and clinical features of organic acidemias: A hospital-based study in a single center in Damascus, Syria. Qatar Med J 2015; 2015(1): 9. DOI: 10.5339/qmj.2015.9Shennar H.K., Al-Asmar D., Kaddoura A., Al-Fahoum S. Diagnosis and clinical features of organic acidemias: A hospital-based study in a single center in Damascus, Syria. Qatar Med J 2015; 2015(1): 9. DOI: 10.5339/qmj.2015.9Urea Cycle Disorders Conference Group: Consensus statement from a conference for the management of patients with urea cycle disorders. J Pediatr 2001; 138: S1–S5.Urea Cycle Disorders Conference Group: Consensus statement from a conference for the management of patients with urea cycle disorders. J Pediatr 2001; 138: S1–S5.Valayannopoulos V., Baruteau J., Delgado M.B., Cano A., Couce M.L., Del Toro M. et al. Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: a retrospective observational study. Orphanet J Rare Dis 2016; 11: 32. DOI: 10.1186/s13023-016-0406-2Valayannopoulos V., Baruteau J., Delgado M.B., Cano A., Couce M.L., Del Toro M. et al. Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: a retrospective observational study. Orphanet J Rare Dis 2016; 11: 32. DOI: 10.1186/s13023-016-0406-2Dixon M., MacDonald A., White F.J. Disorders of Amino Acid Metabolism, Organic Acidaemias and Urea Cycle Disorders. In: Clinical Paediatric Dietetics. S.V. Hoboken (ed.). 5th edition. NJ: Wiley-Blackwell, 2020; 689.Dixon M., MacDonald A., White F.J. Disorders of Amino Acid Metabolism, Organic Acidaemias and Urea Cycle Disorders. In: Clinical Paediatric Dietetics. S.V. Hoboken (ed.). 5th edition. NJ: Wiley-Blackwell, 2020; 689.Uchino T., Endo F., Matsuda I. Neurodevelopmental outcome of longterm therapy of urea cycle disorders in Japan, J Inherit Metab Dis 1998; 21: 151–159. DOI: 10.1023/a:1005374027693Uchino T., Endo F., Matsuda I. Neurodevelopmental outcome of longterm therapy of urea cycle disorders in Japan, J Inherit Metab Dis 1998; 21: 151–159. DOI: 10.1023/a:1005374027693Bachmann C. Outcome and survival of 88 patients with urea cycle disorders: A retrospective evaluation. Eur J Pediatr 2003; 162: 410–416. DOI: 10.1007/s00431-003-1188-9Bachmann C. Outcome and survival of 88 patients with urea cycle disorders: A retrospective evaluation. Eur J Pediatr 2003; 162: 410–416. DOI: 10.1007/s00431-003-1188-9

The authors declare that there are no conflicts of interest present.