Summary
We describe the first two unrelated Spanish patients with creatine transporter deficiency initially identified by brain proton magnetic resonance spectroscopy (MRS). The clinical phenotype was characterized by severe mental retardation, epilepsy, autism, severe speech delay and absence of brain creatine by MRS. Urine creatine/creatinine ratio was increased and creatine uptake in fibroblasts was impaired in both patients. On DNA sequence analysis of the SLC6A8/creatine transporter gene, one hemizygous mutation was found in each patient: one mutation was novel and consisted of a deletion of two nucleotides c.878–879delTC in exon 5, resulting in a frameshift (p.Lys293fsX3), and in the other patient a known deletion of three nucleotides 1222–1224delTTC in exon 8 resulting in p.Phe408del. Creatine treatment for one year failed to improve the neurological symptoms and was associated with a striking increase in body weight in both patients (13 and 16 kg, respectively).
Similar content being viewed by others
References
Almeida LS, Verhoeven NM, Roos B, et al (2004) Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport. Mol Genet Metab 82: 214–219.
Arias A, Garcia-Villoria J, Ribes A (2004) Guanidinoacetate and creatine/creatinine levels in controls and patients with urea cycle defects. Mol Genet Metab 82: 220–223.
Bianchi MC, Tosseti M, Fornai F, et al (2000) Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann Neurol 47: 511–513.
Bizzi A, Bugiani M, Salomons GS, et al (2002) X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8. Ann Neurol 52: 227–231.
Cecil KM, Salomons GS, Ball WS Jr, et al (2001) Irreversible brain creatine deficiency with elevated serum and urine creatine: a creatine transporter defect? Ann Neurol 49: 401–404.
deGrauw TJ, Salomons GS, Cecil KM, et al (2002) Congenital creatine transporter deficiency. Neuropediatrics 33: 232–238.
deGrauw TJ, Cecil KM, Byars AW, et al (2003) The clinical syndrome of creatine transporter deficiency. Mol Cell Biochem 244: 45–48.
Hahn KA, Salomons GS, Tackels-Horne D, et al (2002) X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28. Am J Hum Genet 70: 1349–1356.
Kutz MR, Gunter MJ (2003) Creatine monohydrate supplementation on body weight and percent body fat. J Strength Cond Res 17: 817–821.
Mancini GM, Catsman-Berrevoets CE, de Coo IF, et al (2005) Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families. Am J Med Genet A 132: 288–295.
Rosenberg EH, Almeida LS, Kleefstra T, et al (2004) High prevalence of SLC6A8 deficiency in X-linked mental retardation. Am J Hum Genet 75: 97–105.
Salomons GS, van Dooren SJ, NM Verhoeven, et al (2001) X-linked creatine transporter (SLC6A8 gene) defect: a new creatine deficiency syndrome. Am J Hum Genet 68: 1497–1500.
Salomons GJ, van Dooren SJM, Verhoeven NM, et al (2003) X-linked creatine transporter defect: an overview. J Inherit Metab Dis 26: 309–318.
Stöckler S, Holzbach U, Hanefeld F, et al (1994) Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 36: 409–413.
Stöckler S, Hanefeld F, Frahm J (1996) Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348: 789–790.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicating editor: Michael Gibson
Competing interests: None declared
Rights and permissions
About this article
Cite this article
Póo-Argüelles, P., Arias, A., Vilaseca, M.A. et al. X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism. J Inherit Metab Dis 29, 220–223 (2006). https://doi.org/10.1007/s10545-006-0212-4
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10545-006-0212-4