X-Linked Creatine-Transporter Gene ( SLC6A8) Defect: A New Creatine-Deficiency Syndrome

• Published in: American journal of human genetics Vol. 68; no. 6; pp. 1497 - 1500
• Main Authors: Salomons, Gajja S., van Dooren, Silvy J.M., Verhoeven, Nanda M., Cecil, Kim M., Ball, William S., Degrauw, Ton J., Jakobs, Cornelis
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.06.2001; University of Chicago Press; The American Society of Human Genetics
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Child; Chromosome Mapping; Codon, Nonsense - genetics; Creatine - analysis; Creatine - blood; Creatine - deficiency; Creatine - urine; Developmental Disabilities - genetics; Errors of metabolism; Female; Fibroblasts; Genetic Linkage - genetics; Heterozygote; Humans; Intellectual Disability - genetics; Male; Medical sciences; Membrane Transport Proteins; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Molecular Sequence Data; Muscle Hypotonia - genetics; Pedigree; SLC6A8 gene; Syndrome; X Chromosome - genetics; Sex linked character; Pathogenesis; Muscular hypotonia; Biochemistry; Developmental disorder; Creatine; Genetic determinism; Gene; Learning disability; X-Chromosome; Carrier; Neurological disorder; Carrier protein; Human; Nervous system diseases; Family study; Deficiency; Metabolic diseases; Muscle tonus alteration; Exploration; Genetic disease; Case study; Striated muscle disease; Phenotype; Mutation
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/320595

We report the first X-linked creatine-deficiency syndrome caused by a defective creatine transporter. The male index patient presented with developmental delay and hypotonia. Proton magnetic-resonance spectroscopy of his brain revealed absence of the creatine signal. However, creatine in urine and plasma was increased, and guanidinoacetate levels were normal. In three female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present, to various extents. Fibroblasts from the index patient contained a hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine uptake. The three female relatives were heterozygous for this mutation in SLC6A8, which has been mapped to Xq28.