Browse > Article
http://dx.doi.org/10.5734/JGM.2021.18.1.44

Case report of cerebral creatine deficiency syndrome with novel mutation of SLC6A8 gene in a male child in Bangladesh  

Rahman, Muhammad Mizanur (Department of Pediatric Neurology, Bangabandhu Sheikh Mujib Medical University)
Fatema, Kanij (Department of Pediatric Neurology, Bangabandhu Sheikh Mujib Medical University)
Publication Information
Journal of Genetic Medicine / v.18, no.1, 2021 , pp. 44-47 More about this Journal
Abstract
Cerebral creatine deficiency syndrome (CCDS) is a disorder where a defect is present in transport of creatine in the brain. Creatine plays an essential role in the energy metabolism of the brain. This is a genetic disorder, autosomal recessive or X linked, characterized by intellectual disability, speech and language delay, epilepsy, hypotonia, etc. Until recently very few number of cases have been reported. Here we report a case of 1.5-year-old boy who had epilepsy (epileptic spasm and generalized tonic clonic seizure), intellectual disability, microcephaly, hypotonia and speech delay. His magnetic resonance imaging of brain showed cortical atrophy and electroencephalography showed burst suppression pattern. The diagnosis was confirmed by clinical exome sequencing which showed novel mutation of SLC6A8+ in exon 9, suggestive of X linked recessive CCDS. The patient was then treated with glycine, L-arginine and creatine monohydrate with multiple antiepileptic drugs.
Keywords
Cerebral creatine deficiency syndrome; SLC6A8 protein; Intellectual disability;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Stockler S, Schutz PW, Salomons GS. Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem 2007;46:149-66.   DOI
2 Comeaux MS, Wang J, Wang G, Kleppe S, Zhang VW, Schmitt ES, et al. Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes. Mol Genet Metab 2013;109:260-8.   DOI
3 Item CB, Stockler-Ipsiroglu S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC, et al. Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet 2001;69:1127-33.   DOI
4 Stockler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K. Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet 1996;58:914-22.
5 Freed D, Aldana R, Weber JA, Edwards JS. The sentieon genomics tools - a fast and accurate solution to variant calling from nextgeneration sequence data. bioRxiv 2017, in press.
6 McLaren W, Pritchard B, Rios D, Chen Y, Flicek P, Cunningham F. Deriving the consequences of genomic variants with the Ensembl API and SNP effect predictor. Bioinformatics 2010;26:2069-70.   DOI
7 Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, et al. Ensembl 2018. Nucleic Acids Res 2018;46:D754-61.   DOI
8 Plagnol V, Curtis J, Epstein M, Mok KY, Stebbings E, Grigoriadou S, et al. A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics 2012;28:2747-54.   DOI
9 Mercimek-Andrews S, Salomons GS. Creatine deficiency syndromes. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, eds. GeneReviews®. Seattle (WA): University of Washington, 2009.
10 Salomons GS, van Dooren SJ, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ, et al. X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. Am J Hum Genet 2001;68:1497-500.   DOI
11 van de Kamp JM, Mancini GM, Salomons GS. X-linked creatine transporter deficiency: clinical aspects and pathophysiology. J Inherit Metab Dis 2014;37:715-33.   DOI
12 Clark AJ, Rosenberg EH, Almeida LS, Wood TC, Jakobs C, Stevenson RE, et al. X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology. Hum Genet 2006;119:604-10.   DOI
13 Wang Q, Yang J, Liu Y, Li X, Luo F, Xie J. A novel SLC6A8 mutation associated with intellectual disabilities in a Chinese family exhibiting creatine transporter deficiency: case report. BMC Med Genet 2018;19:193.   DOI
14 Mancardi MM, Caruso U, Schiaffino MC, Baglietto MG, Rossi A, Battaglia FM, et al. Severe epilepsy in X-linked creatine transporter defect (CRTR-D). Epilepsia 2007;48:1211-3.   DOI
15 Pyne-Geithman GJ, deGrauw TJ, Cecil KM, Chuck G, Lyons MA, Ishida Y, et al. Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: a case study. Mol Cell Biochem 2004;262:35-9.   DOI
16 Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 2016;44:D862-8.   DOI
17 Stockler-Ipsiroglu S, Mercimek-Mahmutoglu GS, Salomons GS. Creatine deficiency syndromes. In: Saudubray JM, van den Berghe G, Pagon RA, Walter JH, eds. Inborn metabolic diseases. Berlin: SpringerVerlag Berlin Heidelberg, 2012.
18 Braissant O, Bachmann C, Henry H. Expression and function of AGAT, GAMT and CT1 in the mammalian brain. Subcell Biochem 2007;46:67-81.   DOI
19 Mercimek-Andrews S, Salomons GS. Creatine deficiency syndromes. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, eds. GeneReviews®. Seattle (WA): University of Washington, 2015.
20 deGrauw TJ, Cecil KM, Byars AW, Salomons GS, Ball WS, Jakobs C. The clinical syndrome of creatine transporter deficiency. Mol Cell Biochem 2003;244:45-8.   DOI