Severe Hyperammonaemia with Metabolic Acidosis in a Neonate: a Case Report of Ornithine Transcarbamylase Deficiency (OTCD)
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https://doi.org/10.33102/mjosht.v8i1.209Keywords:
urea cycle disorder, OTC, hyperammonaemia, neonateAbstract
Ornithine transcarbamylase (OTC) deficiency (OTCD), the most common urea cycle disorder, is an X-linked genetic disorder due to complete or partial lack of the OTC enzyme. Its clinical presentation depends on the degree of enzyme deficiency and ranges from an acute neonatal metabolic crisis with a high mortality rate through to an asymptomatic adult. We present a case of a newborn baby boy who presented with poor feeding, vomiting, lethargy, and respiratory distress. Laboratory investigations revealed severe hyperammonaemia, hyperglutaminaemia, hyperalaninaemia, absence of citrulline, and marked orotic aciduria. Family screening confirmed the presence of an OTC disease-causing mutation in his mother. It was a heterozygous mutation, c.316G>A. p. Gly106Arg in exon 4.
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Nagata, N., I. Matsuda, and K. Oyanagi, Estimated frequency of urea cycle enzymopathies in Japan. American Journal of Medical Genetics Part A, 1991. 39(2): p. 228-229. doi: 10.1002/ajmg.1320390226
McCullough, B.A., et al., Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype. American Journal of Medical Genetics Part A, 2000. 93(4): p. 313-319. doi: 10.1002/1096-8628(20000814)93:4<313::AID-AJMG11>3.0.CO;2-M
Gordon, N., Ornithine transcarbamylase deficiency: a urea cycle defect. European Journal of Paediatric Neurology, 2003. 7(3): p. 115-121. doi: 10.1016/S1090-3798(03)00040-0
Batshaw, M.L., Hyperammonemia. Current problems in pediatrics, 1984. 14(11): p. 6-69. doi: 10.1016/0045-9380(84)90047-1
Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr. 1996; 43:127–70.
Brassier A, Gobin S, Arnoux JB, et al. Long-term outcomes in Ornithine Transcarbamylase deficiency: a series of 90 patients. Orphanet J Rare Dis. 2015; 10:58. Published 2015 May 10. doi: 10.1186/s13023-015-0266-1
Tchan, M., Hyperammonemia and lactic acidosis in adults: Differential diagnoses with a focus on inborn errors of metabolism. Reviews in Endocrine and Metabolic Disorders, 2018: p. 1-11. doi: 10.1007/s11154-018-9444-5
Mew, N.A., et al., Urea cycle disorders overview, in GeneReviews®[Internet]. 2017, University of Washington, Seattle.
Caldovic, L., et al., Genotype–phenotype correlations in ornithine transcarbamylase deficiency: a mutation update. Journal of Genetics and Genomics, 2015. 42(5): p. 181-194. doi: 10.1016/j.jgg.2015.04.003
Caldovic, L., et al., Genotype–phenotype correlations in ornithine transcarbamylase deficiency: a mutation update. Journal of Genetics and Genomics, 2015. 42(5): p. 181-194. doi: 10.1016/j.jgg.2015.04.003
Albrecht, J., M. Zielinska, and M.D. Norenberg, Glutamine as a mediator of ammonia neurotoxicity: a critical appraisal. Biochemical pharmacology, 2010. 80(9): p. 1303-1308. doi: 10.1016/j.bcp.2010.07.024
Takanashi, J.-i., et al., Brain MR imaging in acute hyperammonemic encephalopathy arising from late-onset ornithine transcarbamylase deficiency. American journal of neuroradiology, 2003. 24(3): p. 390-393.
Venkateswaran, L., et al., Ornithine transcarbamylase deficiency: a possible risk factor for thrombosis. Pediatric blood & cancer, 2009. 53(1): p. 100-102. doi: 10.1002/pbc.22016
Ali, E.Z., et al., Mutation Study of Malaysian Patients with Ornithine Transcarbamylase Deficiency: Clinical, Molecular, and Bioinformatics Analyses of Two Novel Missense Mutations of the OTC Gene. BioMed research international, 2018. doi: 10.1155/2018/4320831
Ana Isabel Sanchez, Alejandra Rincon, Mary Garcia and Fernando Suarez-Obando., Case Report Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC gene-Expanding the Clinical Phenotype. Case Reports in Genetics, 2017 (3):1-3 doi: 10.1155/2017/1048717
Loscalzo, J., Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circulation research, 2001. 88(8): p. 756-762. doi: 10.1161/hh0801.089861
Maestri, N.E., D. Clissold, and S.W. Brusilow, Neonatal onset ornithine transcarbamylase deficiency: a retrospective analysis. The Journal of pediatrics, 1999. 134(3): p. 268-272. doi: 10.1016/S0022-3476(99)70448-8
Braissant, O., V.A. McLin, and C. Cudalbu, Ammonia toxicity to the brain. Journal of inherited metabolic disease, 2013. 36(4): p. 595-612. doi: 10.1007/s10545-012-9546-2
Albrecht J. (2007) 12 Ammonia Toxicity in the Central Nervous System. In: Lajtha A., Oja S.S., Schousboe A., Saransaari P. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. doi: 10.1007/978-0-387-30373-4_12
Cunningham SC, Kok CY, Dane AP, et al. Induction and prevention of severe hyperammonemia in the spfash mouse model of ornithine transcarbamylase deficiency using shRNA and rAAV-mediated gene delivery. Mol Ther. 2011;19(5):854–859. doi: 10.1038/mt.2011.32
Cunningham SC, Siew SM, Hallwirth CV, et al. Modeling correction of severe urea cycle defects in the growing murine liver using a hybrid recombinant adeno-associated virus/piggyBac transposase gene delivery system. Hepatology. 2015;62(2):417–428. doi: 10.1002/hep.27842
Wenum M, Adam AA, Hakvoort TB, et al. Selecting cells for bioartificial liver devices and the importance of a 3D culture environment: a functional comparison between the HepaRG and C3A cell lines. Int J Biol Sci. 2016;12(8):964–978 doi: 10.7150/ijbs.15165
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