Are cerebral creatine deficiency syndromes on the radar screen?

Cerebral creatine deficiency syndromes (CCDS) are responsible for a considerable proportion of the population affected with mental retardation. CCDS are caused by either an inborn error of the proteins involved in creatine biosynthesis or in the creatine transporter. Besides mental retardation, the clinical characteristics of CCDS are speech and language delay, epilepsy and features of autism. CCDS can be diagnosed by proton magnetic resonance spectroscopy of the brain and/or by biochemical and molecular analysis. Treatment of the defects in creatine biosynthesis has yielded favorable outcomes, while treatments for creatine transporter deficiency are still under investigation at this time. The relatively large contribution of the CCDS to the monogenic causes of mental retardation emphasizes the importance of including CCDS in the differential diagnosis of mental retardation of unknown etiology. Pathophysiology is not yet unravelled, although it is known that creatine plays an important role in energy storage and transmission. Moreover, in vitro data indicate that creatine acts as a neuromodulator in the brain.