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Long-term Clinical Consequences in Patients with Urea Cycle Disorders in Korea: A Single-center Experience  

Lee, Jun (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital)
Kim, Min-ji (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital)
Yoo, Sukdong (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital)
Yoon, Ju Young (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital)
Kim, Yoo-Mi (Department of Pediatrics, Chungnam National University Sejong Hospital)
Cheon, Chong Kun (Division of Medical Genetics and Metabolism, Department of Pediatrics, Pusan National University Children's Hospital)
Publication Information
Journal of The Korean Society of Inherited Metabolic disease / v.21, no.1, 2021 , pp. 15-21 More about this Journal
Abstract
Purpose: Urea cycle disorder (UCD) is an inherited inborn error of metabolism, acting on each step of urea cycle that cause various phenotypes. The purpose of the study was to investigate the long-term clinical consequences in different groups of UCD to characterize it. Methods: Twenty-two patients with UCD genetically confirmed were enrolled at Pusan National University Children's hospital and reviewed clinical features, biochemical and genetic features retrospectively. Results: UCD diagnosed in the present study included ornithine transcarbamylase deficiency (OTCD) (n=10, 45.5%), argininosuccinate synthase 1 deficiency (ASSD) (n=6, 27.3%), carbamoyl-phosphate synthetase 1 deficiency (CPS1D) (n=3, 13.6%), hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS) (n=2, 9.1%), and arginase-1 deficiency (ARG1D) (n=1, 4.5%). The age at the diagnosis was 32.7±66.2 months old (range 0.1 to 228.0 months). Eight (36.4%) patients with UCD displayed short stature. Neurologic sequelae were observed in eleven (50%) patients with UCD. Molecular analysis identified 37 different mutation types (14 missense, 6 nonsense, 6 deletion, 6 splicing, 3 delins, 1 insertion, and 1 duplication) including 14 novel variants. Progressive growth impairment and poor neurological outcomes were associated with plasma isoleucine and leucine concentrations, respectively. Conclusion: Although combinations of treatments such as nutritional restriction of proteins and use of alternative pathways for discarding excessive nitrogen are extensively employed, the prognosis of UCD remains unsatisfactory. Prospective clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth or neurological outcomes and decrease metabolic crisis episodes in patients with UCD.
Keywords
Urea cycle disorder; Clinical consequences; Neurologic outcomes; Branched-chain amino acid;
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1 Harris RA, Joshi M, Jeoung NH, Obayashi M. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. J Nutr 2005;135:1527S-30S.   DOI
2 Shih YT, Huang TN, Hu HT, Yen TL, Hsueh YP. Vcp Overexpression and Leucine Supplementation Increase Protein Synthesis and Improve Fear Memory and Social Interaction of Nf1 Mutant Mice. Cell Rep 2020;31:107835.   DOI
3 Cole JT, Mitala CM, Kundu S, Verma A, Elkind JA, Nissim I, et al. Dietary branched chain amino acids ameliorate injury-induced cognitive impairment. Proc Natl Acad Sci U S A 2010;107:366-71.   DOI
4 Molema F, Gleich F, Burgard P, van der Ploeg AT, Summar ML, Chapman KA, et al. Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment. Mol Genet Metab 2019;126:397-405.   DOI
5 Summar ML, Mew NA. Inborn errors of metabolism with hyperammonemia: urea cycle defects and related disorders. Pediatric Clinics 2018;65:231-46.
6 Rossignol F, Mew NA, Meltzer MR, Gropman AL. Urea cycle disorders. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease: Elsevier, 2020:827-48.
7 Haberle 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
8 Haberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision. J Inherit Metab Dis 2019;42:1192-230.   DOI
9 Adam S, Almeida MF, Assoun M, Baruteau J, Bernabei SM, Bigot S, et al. Dietary management of urea cycle disorders: European practice. Mol Genet Metab 2013;110:439-45.   DOI
10 Posset R, Garcia-Cazorla A, Valayannopoulos V, Teles EL, Dionisi-Vici C, Brassier A, et al. Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders. J Inherit Metab Dis 2016;39:661-72.   DOI
11 Posset R, Garbade SF, Gleich F, Gropman AL, de Lonlay P, Hoffmann GF, et al. Long-term effects of medical management on growth and weight in individuals with urea cycle disorders. Scientific Reports 2020;10:1-13.   DOI
12 Adam S, Champion H, Daly A, Dawson S, Dixon M, Dunlop C, et al. Dietary management of urea cycle disorders: UK practice. J Hum Nutr Diet 2012;25:398-404.   DOI