A novel SLC6A8 mutation associated with motor dysfunction in a child exhibiting creatine transporter deficiency

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Creatine transporter (CT) deficiency is a rare X-linked disorder.
• It results from mutations in the SLC6A8 gene, impacting creatine uptake in the brain.
• This deficiency can lead to intellectual disability and other neurological issues.

Purpose of the Study:

• To describe the clinical, biochemical, and molecular findings in a child with X-linked cerebral creatine deficiency.
• To identify the specific genetic mutation responsible for the condition in the patient.
• To emphasize the importance of considering CT deficiency in the differential diagnosis of intellectual disability in males.

Main Methods:

• Clinical examination of the patient.
• Biochemical analysis, including urinary creatine/creatinine ratio.
• Brain proton magnetic resonance spectroscopy (MRS).
• Molecular genetic analysis of the SLC6A8 gene.
• Assessment of creatine transport function.

Main Results:

• The patient presented with symptoms consistent with cerebral creatine deficiency.
• Biochemical tests showed an increased urinary creatine/creatinine ratio.
• Brain MRS revealed abnormal findings.
• Reduced creatine transport was confirmed.
• A novel, hemizygous mutation in the SLC6A8 gene was identified in the child, absent in the mother.

Conclusions:

• The findings confirm a diagnosis of X-linked creatine transporter deficiency.
• The novel SLC6A8 mutation is the likely cause of the disorder in this patient.
• CT deficiency should be considered in the diagnostic workup of males presenting with mental retardation and related neurological symptoms.