Subject(s)
Dystonic Disorders/genetics , Dystonic Disorders/metabolism , Genetic Predisposition to Disease/genetics , Parkinsonian Disorders/genetics , Parkinsonian Disorders/metabolism , Sodium-Potassium-Exchanging ATPase/genetics , Acute Disease , Age of Onset , Amino Acid Substitution/genetics , Brain/diagnostic imaging , Brain/metabolism , Brain/physiopathology , Child , DNA Mutational Analysis , Deglutition Disorders/genetics , Deglutition Disorders/physiopathology , Disease Progression , Dystonic Disorders/physiopathology , Genetic Markers/genetics , Genotype , Humans , Male , Muscle Hypotonia/genetics , Muscle Hypotonia/physiopathology , Mutation , Parkinsonian Disorders/physiopathology , Positron-Emission TomographyABSTRACT
We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation, absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation and was discovered upon subsequent review of the MRS. Molecular studies showed large genomic deletions of a large part of the 3' end of the complete open reading frame of the SLC6A8 gene. This report emphasizes the importance of MRS in evaluating neurological symptoms, broadens the phenotypic spectrum of CRTR and adds knowledge about the pathogenesis of creatine depletion in the brain and retina.
