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X -linked mental retardation, Creatine Deficiency Syndrome - SLC6A8

Clinical Features

Creatine-transporter (SLC6A8) -deficiency belongs to the cerebral creatine deficiency syndromes (inborn errors of creatine metabolism). SLC6A8 deficiency is inherited in an X-linked manner. The phenotype of SLC6A8 deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, and behavior disorder. General developmental delay, hyperactivity, and speech delay are usually evident by age of two years. Various types of epilepsy affect a large proportion of males with SLC6A8 deficiency. Females heterozygous for SLC6A8 deficiency may have learning and behavioral problems. For diagnosis, measurement of creatin to creatinine in urine may be helpful. However, this test is not as reliable, since not all patients are detected, especially girls presenting with normal creatin/creatinine-ratio in urine.

As 2.1% of males with nonsyndromic X-linked intellectual disability have SLC6A deficiency, all mentally retarded males in the absence of a confirmed alternative diagnosis should be tested for SLC6A8. 

Genetic Information

The SLC6A8 protein is a member of a solute carrier family of Na- and Cl- dependent transporters responsible for the uptake of certain neurotransmitters and amino acids. Pathogenic mutations cause impaired creatine uptake in fibroblasts.

Prevalence

2.1% of males with nonsyndromic X-linked intellectual disability.

Diagnostic