Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect

Recently, 3 patients with a creatine synthesis defect have been described. They presented with developmental regression, extrapyramidal movement abnor malities, and intractable epilepsy, and they improved with treatment of cre atine monohydrate. We report 2 unrelated boys with a creatine synthesis def ect and nonspecific presenting signs of psychomotor retardation, behavioral problems, and, in 1, mild epilepsy. Metabolic urine screening revealed ele vations in all metabolites, expressed as millimoles per mole of creatinine, which suggests decreased creatinine excretion. This finding led to the cor rect diagnosis. We propose to include the assessment of the overall concent rations of amino acids and organic acids relative to creatinine in routine metabolic urine screening.