X-linked creatine transporter defect: a report on two unrelated boys with a severe clinical phenotype

Abstract

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.

Fig. 1

MRS images showing classical absence of creatine peak (arrow) in case 1 (a) and case 2 (b)

Fig. 2

Fundus photograph, right eye, patient 2. At the equator, 360°, was a band of diffuse granular pigmentation (arrow). This pigmentation and mild attenuation of the retinal arterioles and mild pallor of the optic nerve head were consistent with early retinal degeneration. Features of the left fundus were similar