Creatine Research Today is a free monthly online journal that collates and summarizes the latest research about Creatine, including details on supplements, side-effects, benefits, dangers, muscle growth.

GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis.

Mercimek-Mahmutoglu S, Stoeckler-Ipsiroglu S, Adami A, Appleton R, Araújo HC, Duran M, Ensenauer R, Fernandez-Alvarez E, Garcia P, Grolik C, Item CB, Leuzzi V, Marquardt I, Mühl A, Saelke-Kellermann RA, Salomons GS, Schulze A, Surtees R, van der Knaap MS, Vasconcelos R, Verhoeven NM, Vilarinho L, Wilichowski E, Jakobs C

Division of Biochemical Diseases, British Columbia Children's Hospital, Vancouver, Canada.

BACKGROUND: Guanidinoactetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis. The authors analyzed clinical, biochemical, and molecular findings in 27 patients. METHODS: The authors collected data from questionnaires and literature reports. A score including degree of intellectual disability, epileptic seizures, and movement disorder was developed and used to classify clinical phenotype as severe, moderate, or mild. Score and biochemical data were assessed before and during treatment with oral creatine substitution alone or with additional dietary arginine restriction and ornithine supplementation. RESULTS: Intellectual disability, epileptic seizures, guanidinoacetate accumulation in body fluids, and deficiency of brain creatine were common in all 27 patients. Twelve patients had severe, 12 patients had moderate, and three patients had mild clinical phenotype. Twenty-one of 27 (78%) patients had severe intellectual disability (estimated IQ 20 to 34). There was no obvious correlation between severity of the clinical phenotype, guanidinoacetate accumulation in body fluids, and GAMT mutations. Treatment resulted in almost normalized cerebral creatine levels, reduced guanidinoacetate accumulation, and in improvement of epilepsy and movement disorder, whereas the degree of intellectual disability remained unchanged. CONCLUSION: Guanidinoactetate methyltransferase deficiency should be considered in patients with unexplained intellectual disability, and urinary guanidinoacetate should be determined as an initial diagnostic approach.

Published 8 August 2006 in Neurology, 67(3): 480-4.
Full-text of this article is available online (may require subscription).

© 2004-2008 Creatine Research Today. All Rights Reserved.