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Case Report

Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report

  • Authors:
    • Jun Xu
    • Aimin Zhang
    • Furong Huang
  • View Affiliations / Copyright

    Affiliations: Department of Neonatology, Children's Medical Center, Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
  • Pages: 623-629
    |
    Published online on: May 6, 2020
       https://doi.org/10.3892/etm.2020.8717
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Abstract

The aim of the present report was to describe the clinical presentation, diagnosis, and treatment of a case of carbamoyl phosphate synthetase 1 (CPS1) deficiency in a neonate, specifically, a 3 day‑old female who visited Hunan Provincial People's Hospital due to anorexia and lethargy for 1 day. Physical and laboratory examination, and MRI were undertaken. Whole exome sequencing (WES) was applied for molecular etiology identification. Sanger sequencing was utilized to validate the variants detected by WES. Structural modeling was conducted for pathogenic analysis. Clinical examination revealed increased intracranial pressure, hyperammonemia, reduced citrulline, and increased glutamic acid levels. WES identified compound heterozygosity of c.713G>C, p.Arg238Pro and c.2339G>A, p.Arg780His in CPS1 (NCBI reference sequence, NM_001875.4) as candidate pathogenic variants. Sanger sequencing validated these variants. Structural modeling further confirmed the pathogenesis of these mutations. In conclusion, CPS1 deficiency in neonates is a serious condition that may be misdiagnosed due to severe infection. WES can be a helpful tool in facilitating the diagnosis of this disease.
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1 

Soria LR, Allegri G, Melck D, Pastore N, Annunziata P, Paris D, Polishchuk E, Nusco E, Thöny B, Motta A, et al: Enhancement of hepatic autophagy increases ureagenesis and protects against hyperammonemia. Proc Natl Acad Sci U S A. 115:391–396. 2018.PubMed/NCBI View Article : Google Scholar

2 

Ballantyne LL, Sin YY, St Amand T, Si J, Goossens S, Haenebalcke L, Haigh JJ, Kyriakopoulou L, Schulze A and Funk CD: Strategies to rescue the consequences of inducible arginase-1 deficiency in mice. PLoS One. 10(e0125967)2015.PubMed/NCBI View Article : Google Scholar

3 

Braissant O: Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab. 100 (Suppl 1):S3–S12. 2010.PubMed/NCBI View Article : Google Scholar

4 

Unsinn C, Das A, Valayannopoulos V, Thimm E, Beblo S, Burlina A, Konstantopoulou V, Mayorandan S, de Lonlay P, Rennecke J, et al: Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001-2013. Orphanet J Rare Dis. 11(116)2016.PubMed/NCBI View Article : Google Scholar

5 

Summar ML, Dasouki MJ, Schofield PJ, Krishnamani MR, Vnencak-Jones C, Tuchman M, Mao J and Phillips JA 3rd: Physical and linkage mapping of human carbamyl phosphate synthetase I (CPS1) and reassignment from 2p to 2q35. Cytogenet Cell Genet. 71:266–267. 1995.PubMed/NCBI View Article : Google Scholar

6 

Haberle J, Schmidt E, Pauli S, Rapp B, Christensen E, Wermuth B and Koch HG: Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset. Hum Mutat. 21(444)2003.PubMed/NCBI View Article : Google Scholar

7 

Funghini S, Donati MA, Pasquini E, Zammarchi E and Morrone A: Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions. Hum Mutat. 22:340–341. 2003.PubMed/NCBI View Article : Google Scholar

8 

Summar ML, Hall LD, Eeds AM, Hutcheson HB, Kuo AN, Willis AS, Rubio V, Arvin MK, Schofield JP and Dawson EP: Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene. Gene. 311:51–57. 2003.PubMed/NCBI View Article : Google Scholar

9 

Singh RH: Nutritional management of patients with urea cycle disorders. J Inherit Metab Dis. 30:880–887. 2007.PubMed/NCBI View Article : Google Scholar

10 

World Medical Association. World medical association declaration of helsinki: Ethical principles for medical research involving human subjects. JAMA. 310:2191–2194. 2013.PubMed/NCBI View Article : Google Scholar

11 

Jin D, Yu T, Zhang L, Wang T, Hu J, Wang Y and Yang XA: Novel NFU1 variants induced MMDS behaved as special leukodystrophy in chinese sufferers. J Mol Neurosci. 62:255–261. 2017.PubMed/NCBI View Article : Google Scholar

12 

Peng F, Zhong L, Zhang B, Zou R, Nie S, Tian X, Deng S and He X: Successful application of next-generation sequencing for pre-natal diagnosis in a pedigree with chronic granulomatosis disease. Exp Ther Med. 17:2931–2936. 2019.PubMed/NCBI View Article : Google Scholar

13 

Chen Q, Bao H, Wu H, Zhao S, Huang S and Zhao F: Diagnosis of cobalamin C deficiency with renal abnormality from onset in a Chinese child by next generation sequencing: A case report. Exp Ther Med. 14:3637–3643. 2017.PubMed/NCBI View Article : Google Scholar

14 

Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, Johnson DM, Strauss AW, Comeau AM, Eaton RB and Grady GF: Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: A two-year summary from the new England newborn screening program. Clin Chem. 47:1945–1955. 2001.PubMed/NCBI

15 

Adzhubei I, Jordan DM and Sunyaev SR: Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 7(20)2013.PubMed/NCBI View Article : Google Scholar

16 

Kumar P, Henikoff S and Ng PC: Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 4:1073–1081. 2009.PubMed/NCBI View Article : Google Scholar

17 

Choi Y, Sims GE, Murphy S, Miller JR and Chan AP: Predicting the functional effect of amino acid substitutions and indels. PLoS One. 7(e46688)2012.PubMed/NCBI View Article : Google Scholar

18 

Choi Y and Chan AP: PROVEAN web server: A tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics. 31:2745–2747. 2015.PubMed/NCBI View Article : Google Scholar

19 

Schwarz JM, Cooper DN, Schuelke M and Seelow D: MutationTaster2: Mutation prediction for the deep-sequencing age. Nat Methods. 11:361–362. 2014.PubMed/NCBI View Article : Google Scholar

20 

de Cima S, Polo LM, Diez-Fernandez C, Martínez AI, Cervera J, Fita I and Rubio V: Structure of human carbamoyl phosphate synthetase: Deciphering the on/off switch of human ureagenesis. Sci Rep. 5(16950)2015.PubMed/NCBI View Article : Google Scholar

21 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015.PubMed/NCBI View Article : Google Scholar

22 

Kurokawa K, Yorifuji T, Kawai M, Momoi T, Nagasaka H, Takayanagi M, Kobayashi K, Yoshino M, Kosho T, Adachi M, et al: Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency. J Hum Genet. 2:349–354. 2007.PubMed/NCBI View Article : Google Scholar

23 

Liu D, Wang Y, Yang XA and Liu D: De novo mutation of paternal IGF2 gene causing silver-russell syndrome in a sporadic patient. Front Genet. 8(105)2017.PubMed/NCBI View Article : Google Scholar

24 

Haberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Crespo PS, Santer R, et al: Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 7(32)2012.PubMed/NCBI View Article : Google Scholar

25 

Yang X, Shi J, Lei H, Xia B and Mu D: Neonatal-onset carbamoyl phosphate synthetase I deficiency: A case report. Medicine (Baltimore). 96(e7365)2017.PubMed/NCBI View Article : Google Scholar

26 

Ali EZ, Khalid MK, Yunus ZM, Yakob Y, Chin CB, Abd Latif K and Hock NL: Carbamoylphosphate synthetase 1 (CPS1) deficiency: Clinical, biochemical, and molecular characterization in Malaysian patients. Eur J Pediatr. 175:339–346. 2016.PubMed/NCBI View Article : Google Scholar

27 

Haberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M, Mandel H, Martinelli D, Pintos-Morell G, Santer R, et al: Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. 42:1192–1230. 2019.PubMed/NCBI View Article : Google Scholar

28 

Ono H, Suto T, Kinoshita Y, Sakano T, Furue T and Ohta T: A case of carbamoyl phosphate synthetase 1 deficiency presenting symptoms at one month of age. Brain Dev. 31:779–781. 2009.PubMed/NCBI View Article : Google Scholar

29 

Klaus V, Vermeulen T, Minassian B, Israelian N, Engel K, Lund AM, Roebrock K, Christensen E and Häberle J: Highly variable clinical phenotype of carbamylphosphate synthetase 1 deficiency in one family: An effect of allelic variation in gene expression? Clin Genet. 76:263–269. 2009.PubMed/NCBI View Article : Google Scholar

30 

Foschi FG, Morelli MC, Savini S, Dall'Aglio AC, Lanzi A, Cescon M, Ercolani G, Cucchetti A, Pinna AD and Stefanini GF: Urea cycle disorders: A case report of a successful treatment with liver transplant and a literature review. World J Gastroenterol. 21:4063–4068. 2015.PubMed/NCBI View Article : Google Scholar

31 

Kasahara M, Sakamoto S, Shigeta T, Fukuda A, Kosaki R, Nakazawa A, Uemoto S, Noda M, Naiki Y and Horikawa R: Living-donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency. Pediatr Transplant. 14:1036–1040. 2010.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Xu J, Zhang A and Huang F: Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report. Exp Ther Med 20: 623-629, 2020.
APA
Xu, J., Zhang, A., & Huang, F. (2020). Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report. Experimental and Therapeutic Medicine, 20, 623-629. https://doi.org/10.3892/etm.2020.8717
MLA
Xu, J., Zhang, A., Huang, F."Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report". Experimental and Therapeutic Medicine 20.1 (2020): 623-629.
Chicago
Xu, J., Zhang, A., Huang, F."Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report". Experimental and Therapeutic Medicine 20, no. 1 (2020): 623-629. https://doi.org/10.3892/etm.2020.8717
Copy and paste a formatted citation
x
Spandidos Publications style
Xu J, Zhang A and Huang F: Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report. Exp Ther Med 20: 623-629, 2020.
APA
Xu, J., Zhang, A., & Huang, F. (2020). Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report. Experimental and Therapeutic Medicine, 20, 623-629. https://doi.org/10.3892/etm.2020.8717
MLA
Xu, J., Zhang, A., Huang, F."Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report". Experimental and Therapeutic Medicine 20.1 (2020): 623-629.
Chicago
Xu, J., Zhang, A., Huang, F."Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: A case report". Experimental and Therapeutic Medicine 20, no. 1 (2020): 623-629. https://doi.org/10.3892/etm.2020.8717
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