X-linked creatine-transporter gene (SLC6A8) defect: A new creatine-deficiency syndrome

We report the first X-linked creatine-deficiency syndrome caused by a defec tive creatine transporter. The male index patient presented with developmen tal delay and hypotonia. Proton magnetic-resonance spectroscopy of his brai n revealed absence of the creatine signal. However, creatine in urine and p lasma was increased, and guanidinoacetate levels were normal. In three fema le relatives of the index patient, mild biochemical abnormalities and learn ing disabilities were present, to various extents. Fibroblasts from the ind ex patient contained a hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine uptake. The three female relatives were heterozy gous for this mutation in SLC6A8, which has been mapped to Xq28.