X‐linked creatine transporter defect: An overview

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Abstract
Summary: In 2001 we identified a new inborn error of metabolism caused by a defect in the X‐linked creatine transporter SLC6A8 gene mapped at Xq28 (SLC6A8 deficiency, McKusick 300352). An X‐linked creatine transporter defect was presumed because of (1) the absence of creatine in the brain as indicated by proton magnetic resonance spectroscopy (MRS); (2) the elevated creatine levels in urine and normal guanidinoacetate levels in plasma, ruling out a creatine biosynthesis defect; (3) the absence of an improvement on creatine supplementation; and (4) the fact that the pedigree suggested an X‐linked disease. Our hypothesis was proved by the presence of a hemizygous nonsense mutation in the male index patient and by the impaired creatine uptake by cultured fibroblasts. Currently, at least 7 unrelated families (13 male patients and 13 carriers) with a SLC6A8 deficiency have been identified. Four families come fromone metropolitan area. This suggests that SLC6A8 deficiency may have a relatively high incidence. The hallmarks of the disorder are X‐linked mental retardation, expressive speech and language delay, epilepsy, developmental delay and autistic behaviour. In approximately 50% of the female carriers, learning disabilities of varying degrees have been noted.