How to Cite this Article: Ardon O, Amat di San Filippo C, Salomons GS, Longo N. 2010. Creatine transporter deficiency in two half-brothers. Am J Med Genet Part A 152A:1979–1983.
Creatine transporter deficiency in two half-brothers†
Article first published online: 2 JUL 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 8, pages 1979–1983, August 2010
How to Cite
Ardon, O., Filippo, C. A. d. S., Salomons, G. S. and Longo, N. (2010), Creatine transporter deficiency in two half-brothers. Am. J. Med. Genet., 152A: 1979–1983. doi: 10.1002/ajmg.a.33551
- Issue published online: 20 JUL 2010
- Article first published online: 2 JUL 2010
- Manuscript Accepted: 17 MAY 2010
- Manuscript Received: 9 OCT 2009
- creatine transport;
- human fibroblasts;
- creatine transporter deficiency;
- creatine deficiency
X-linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter encoded by the SLC6A8 gene. Here, we report two half-brothers with this condition and characterize creatine transport in human fibroblasts. The propositus presented at 6 months of age with delays in development and slow progress since then with no regression. Seizures started at 3.5 years of age and responded well to treatment with anticonvulsants. He had failure to thrive with all growth parameters (including head size) at or below the fifth centile. Brain MRI indicated hemispheric white matter abnormalities, while MR spectroscopy indicated markedly reduced creatine peak. Biochemical testing indicated increased urine creatine/creatinine ratio, with normal plasma creatine and guanidinoacetate. To confirm the diagnosis, we measured C-creatine transport in fibroblasts. C-Creatine transport in normal human fibroblasts was linear for up to 2 hr at 37°C. Kinetic studies indicated the presence of a single saturable creatine transporter with a Km of 34.7 ± 2.5 µM. Fibroblasts from the propositus lacked creatine transport. DNA testing indicated hemizygosity for a novel deletion producing a frameshift (c.974_975delCA, p.Thr325SerfsX139) in the creatine transporter gene. His 12-year-old half-brother had similar biochemical and clinical abnormalities except for the presence of macrocephaly and the absence of seizures. The mother had history of seizures in childhood, but had normal development. These results show that human fibroblasts have a single major creatine transporter and that measurement of its specific activity can confirm creatine transporter deficiency. © 2010 Wiley-Liss, Inc.