Prevalence: < 1/106. Autosomal recessive transmission of a mutation:

-   of the arginine-glycine amidinotransferase (AGAT, chr 15) which synthesizes guanidinoacetic acid from arginine and glycine [MIM 612 718]

-           or of the guanido-acetate methyltransferase (GTAG, chr 19) that transforms guanidinoacetic acid into creatine [MIM 612 736].

Creatine is an essential part of the muscle and brain tissue: it is a source of energy and has neuromodulator properties by regulating the expression of the post-synaptic GABA receptors. It is either of alimentary origin (50%) or endogenous (liver, kidney, pancreas, some glial cells).

Clinical presentation: moderate to severe intellectual disability and speech and expressive language retardation, dystonia, autistic traits

Diagnosis: decreased creatine level in plasma and urines, absence of creatine by MRI spectroscopy, measurement of enzyme activity on fibroblasts.

Treatment: creatine supplements orally (200 to 400 mg/kg/d); in case of GAMT deficiency, the synthesis of guanidinoacetic acid which is neurotoxic at high concentrations should be reduced by a hypoproteinic diet poor in arginine or enriched in ornithine. This diet is effective against epilepsy and dystonia.

Anesthetic implications: 

intellectual deficit; behavioral disorders, epilepsy, autistic traits

References : 

-        Cheillan D, Cognat S, Vandenberghe N, Des Portes V, Vianey-Saban C.
Les syndromes de déficit en créatine.
Rev Neurol 2005; 3: 284-9.

-        Cano A, Valayannopoulos V.
Nouvelles pathologies,
in Maladies métaboliques héréditaires, édité par Chabrol B et de Lonlay P, Doin 2011, p 159-61

Updated: March 2018