Creatine deficiency syndrome (CDS). Guanidinoacetate methyltransferase (GAMT) deficiency.
Incidence
Very rare. Autosomal recessive disorder of creatine biosynthesis. First case described in 1994. More than 50 cases known with the condition to 2011.
Clinical Characteristics
Main clinical features are mental and motor retardation usually severe, epilepsy and extrapyramidal symptoms. Patients may have hypotonia and autistic features. Main biochemical features are accumulation of guanidinoacetate (the immediate precursor of creatine) in body fluids, low urinary creatinine excretion, and depletion of creatine and creatine-phosphate in the brain as shown by in-vivo MRS. MRS of the brain typically shows marked reduction in the size of the creatine peak. Diagnosis of GAMT deficiency is possible by determination of urinary guanidinoacetate concentration and by the measurement of GAMT activity in fibroblasts or virus transformed lymphoblasts. Prenatal diagnosis is possible (GAMT activity in cultivated amniotic cells). Oral replacement therapy with creatine-monohydrate (350 mg/kg/day) improve the extrapyramidal symptoms and MRI signal abnormalities in the globus pallidus and the abnormal EEG, with normalization of the urinary creatinine excretion, which indicate a restoration of muscle creatine (which account for 90% of total body creatine stores).
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-W, EB-F. EB- amniotic cells. Diagnosis of GAMT deficiency is possible by determination of urinary (but also in plasma and CSF) guanidinoacetate (GAA) concentration by GC/MS and by the measurement of GAMT activity in fibroblasts or virus transformed lymphoblasts. MRS of the brain typically shows marked reduction in the size of the creatine peak.