Abstract This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G > A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.
SUN Wei-Hua,ZHUANG Dan-Yan,WANG Yao et al. Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families[J]. CJCP, 2020, 22(5): 482-487.
SUN Wei-Hua,ZHUANG Dan-Yan,WANG Yao et al. Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families[J]. CJCP, 2020, 22(5): 482-487.
Cecil KM, Salomons GS, Ball WS Jr, et al. Irreversible brain creatine deficiency with elevated serum and urine creatine:a creatine transporter defect?[J]. Ann Neurol, 2001, 49(3):401-404.
[3]
Salomons GS, van Dooren SJ, Verhoeven NM, et al. X-linked creatine-transporter gene (SLC6A8) defect:a new creatine-deficiency syndrome[J]. Am J Hum Genet, 2001, 68(6):1497-1500.
[4]
Wang Q, Yang J, Liu Y, et al. A novel SLC6A8 mutation associated with intellectual disabilities in a Chinese family exhibiting creatine transporter deficiency:case report[J]. BMC Med Genet, 2018, 19(1):193.
Richards S, Aziz N, Bale S, 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[J]. Genet Med, 2015, 17(5):405-424.
[7]
Stockler-Ipsiroglu S, Apatean D, Battini R, et al. Arginine:glycine amidinotransferase (AGAT) deficiency:clinical features and long term outcomes in 16 patients diagnosed worldwide[J]. Mol Genet Metab, 2015, 116(4):252-259.
[8]
Sun W, Wang Y, Zu Z, et al. First reported Chinese case of guanidinoacetate methyltransferase deficiency in a 4-year-old child[J]. Clin Chim Acta, 2017, 470:42-45.
[9]
Dreha-Kulaczewski S, Kalscheuer V, Tzschach A, et al. A novel SLC6A8 mutation in a large family with X-linked intellectual disability:clinical and proton magnetic resonance spectroscopy data of both hemizygous males and heterozygous females[J]. JIMD Rep, 2014, 13:91-99.
[10]
van de Kamp JM, Mancini GM, Salomons GS. X-linked creatine transporter deficiency:clinical aspects and pathophysiology[J]. J Inherit Metab Dis, 2014, 37(5):715-733.
[11]
van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, et al. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency[J]. J Med Genet, 2013, 50(7):463-472.
[12]
DesRoches CL, Patel J, Wang P, et al. Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene[J]. Gene, 2015, 565(2):187-191.
[13]
Clark JF, Cecil KM. Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes[J]. Pediatr Res, 2015, 77(3):398-405.
[14]
Heussinger N, Saake M, Mennecke A, et al. Variable white matter atrophy and intellectual development in a family with X-linked creatine transporter deficiency despite genotypic homogeneity[J]. Pediatr Neurol, 2017, 67:45-52.
Tao D, Leister W, Huang W, et al. Facile high-performance liquid chromatography mass spectrometry method for analysis of cyclocreatine and phosphocyclocreatine in complex mixtures of amino acids[J]. J Agric Food Chem, 2019, 67(25):7190-7196.
[17]
El-Kasaby A, Kasture A, Koban F, et al. Rescue by 4-phenylbutyrate of several misfolded creatine transporter-1 variants linked to the creatine transporter deficiency syndrome[J]. Neuropharmacology, 2019, 161:107572.
[18]
Ullio-Gamboa G, Udobi KC, Dezard S, et al. Dodecyl creatine ester-loaded nanoemulsion as a promising therapy for creatine transporter deficiency[J]. Nanomedicine (Lond), 2019, 14(12):1579-1593.
