Published date: Jan 09 2023

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 20, Issue No. 12

Pages: 1047–1050

DOI: 10.18502/ijrm.v20i12.12567

Maryam Hassanloum.hassanlou@semnan.ac.irFarzanegan Campus, Semnan University, Semnan, Iran.

Maryam AbiriDepartment of Medical Genetics, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Sirous ZeinaliDr. Zeinali’s Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran.

Background: Citrullinemia type 1 is an autosomal recessive disease resulting in ammonia accumulation in the blood, and if uncontrolled may progress to coma or death in the early months after birth.

Cases presentation: 7 families from Southwest Iran having one or more children in their families or relatives, who died in the early months after birth due to citrullinemia type 1 visited for genetic counseling and prenatal diagnosis. Whole-exome sequencing was performed on peripheral blood specimens and chorionic villus samples. Sanger sequencing confirmed the genetic results. Both parents were identified as carriers for the exon 15 c.1168G>A mutation in each family. The fetus in 6 out of 7 families was homozygote for A substitution on the argininosuccinate synthetase 1 gene.

Conclusion: The presence of a common mutation in the argininosuccinate synthetase 1 gene in all affected families of Southwest Iran shows a possible population cluster in this area.

Key words: Argininosuccinate synthetase, Chorionic villus sampling, Point mutation.

[1] Nuciforo S, Heim MH. Organoids to model liver disease. JHEP Rep 2020; 3: 100198.

[2] Zielonka M, Kolker S, Gleich F, Stutzenberger N, Nagamani SCS, Gropman AL, et al. Early prediction of phenotypic severity in citrullinemia type 1. Ann Clin Transl Neurol 2019; 6: 1858-1871.

[3] Kang H, Kim M, Lee JH. Nutritional management in a patient with citrullinemia type 1. Clin Nutr Res 2021; 10: 268-277.

[4] Hayasaka K. Metabolic basis and treatment of citrin deficiency. J Inherit Metab Dis 2021; 44: 110-117.

[5] Szlosarek PW, Steele JP, Nolan L, Gilligan D, Taylor P, Spicer J, et al. Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma: A randomized clinical trial. JAMA Oncol 2017; 3: 58-66.

[6] Ruxmohan S, Quinonez J, Choudhari J, Poudel S, Pandav K. Hyperammonemic encephalopathy in an adolescent patient of citrullinemia type 1 with an atypical presentation. Cureus 2021; 13: e15109.

[7] Lin Y, Gao H, Lu B, Zhou S, Zheng T, Lin W, et al. Citrullinemia type I is associated with a novel splicing variant, c.773 + 4A > C, in ASS1: A case report and literature review. BMC Med Genet 2019; 20: 110.

[8] Randon DN, Sperb-Ludwig F, Vianna FSL, Becker APP, Vargas CR, Sitta A, et al. Prevalence of the most common pathogenic variants in three genes for inborn errors of metabolism associated with sudden unexpected death in infancy: A population-based study in south Brazil. Genet Mol Biol 2020; 43: 20190298.

[9] Diez-Fernandez C, Rufenacht V, Haberle J. Mutations in the human argininosuccinate synthetase (ASS1) gene, impact on patients, common changes, and structural considerations. Hum Mutat 2017; 38: 471-484.

[10] Diez-Fernandez C, Wellauer O, Gemperle C, Rufenacht V, Fingerhut R, Haberle J. Kinetic mutations in argininosuccinate synthetase deficiency: Characterisation and in vitro correction by substrate supplementation. J Med Genet 2016; 53: 710-719.

[11] Pishva N, Mirzaee A, Karamizade Z, Pourarian S, Hemmati F, Razvi M, et al. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism. Iran J Neonat 2015; 5: 11-14.

[12] Diez-Fernandez C, Rufenacht V, Haberle J. Mutations in the human argininosuccinate synthetase (ASS1) gene, impact on patients, common changes, and structural considerations. Hum Mutat 2017; 38: 471-484.

[13] Moarefian Sh, Zamani M, Rahmanifar A, Behnam B, Zaman T. Clinical, laboratory data and outcomes of 17 Iranian citrullinemia type 1 patients: Identification of five novel ASS1 gene mutations. JIMD Rep 2022; 63: 231-239.

[14] Silvera-Ruiz SM, Arranz JA, Haberle J, Angaroni CJ, Bezard M, Guelbert N, et al. Urea cycle disorders in argentine patients: Clinical presentation, biochemical and genetic findings. Orphanet J Rare Dis 2019; 14: 203.

[15] Kose E, Unal O, Bulbul S, Gunduz M, Haberle J, Arslan N. Identification of three novel mutations in fourteen patients with citrullinemia type 1. Clin Biochem 2017; 50: 686-689.

[16] Castellani C, Assael BM. Cystic fibrosis: A clinical view. Cell Mol Life Sci 2017; 74: 129-140.

[17] Venugopal A, Chandran M, Eruppakotte N, Kizhakkillach S, Breezevilla SC, Vellingiri B. Monogenic diseases in India. Mutat Res Rev Mutat Res 2018; 776: 23-31.

[18] Kausar M, Makitie RE, Toiviainen-Salo S, Ignatius J, Anees M, Makitie O. Recessive multiple epiphyseal dysplasia- Clinical characteristics caused by rare compound heterozygous SLC26A2 genotypes. Eur J Med Genet 2019; 62: 103573.

[19] Chakravarti A. Magnitude of mendelian versus complex inheritance of rare disorders. Am J Med Genet A 2021; 185: 3287-3293.