Guanidinoacetate Methyltransferase Deficiency, a Treatable Neurodevelopmental Disorder

Abstract

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive inborn error of creatine synthesis that results in intellectual disability, epilepsy, expressive language delay, and dystonia. We report data from two siblings with an uncommon GAMT deficiency phenotype and their clinical, biochemical, imaging, and treatment findings. The older sibling had intellectual disability, epilepsy, and generalized dystonia. The younger sibling had intellectual disability and generalized dystonia. After treatment with creatine, verbal fluency improved, as well as dystonia and aggression. This study confirms that in patients with unexplained intellectual disability, epilepsy, and/or movement disorders, GAMT deficiency should be considered. GAMT-associated cerebral creatine deficiency syndrome is a potentially treatable condition and can be identified by elevated levels of guanidinoacetate in plasma or urine or by a significantly decreased creatine peak on magnetic resonance spectroscopy.

Keywords

neurogenetics - neurometabolic disorders - pediatric movement disorders - epilepsy - intellectual disability - rare diseases

Publication History

Received: 29 September 2020

Accepted: 24 November 2022

Article published online:
13 January 2023

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