Cerebral creatine transporter deficiency:: An infradiagnosed neurometabolic disease

Introduction. Brain creatine deficiencies are a group of inborn errors of metabolism recently recognized which are caused by arginine: glycine amidinotrans/erase (AGAT) deficiency, guanidinoacetate metiltransferase (GAMT) deficiency and defects in creatine transporter (CRTR). Although all of them arc characterized by a brain creatine deficiency, clinical and biochemical features are different. Case reports. We present a retrospective study about four patients of masculine sex affected of creatine transporter defects who were recently diagnosed in our Centre. We describe the clinical presentation features, the different tests that we used in the diagnosis process (brain magnetic resonance spectroscopy, biochemical analysis of guanidino-acetate and creatine/creatinine ratio in urine), evolution aspects and the response to treatment. The most significative clinical feature was developmental delay mainly in expressive speech, they also presented epilepsy (three cases), autism (three cases), hypotonia (one case) and microcephalia (one case). Brain magnetic resonance spectroscopy, showed a low (three cases) or an absence (one case) of creatine level. To confirm the defect we studied the creatine uptake in fibroblasts and molecular analysis of the SLC6A8/creatine transporter gene. Patients with creatine transporter deficiency arc being treated with arginine, because a lack of response to creatine. Conclusion. Cerebral creatine transporter deficiency can present with different neurological symptoms but developmental and language delay and epilepsy are the most significative; diagnosis is easy and there are some therapeutical options.