Treatment experience in two adults with creatinfe transporter deficiency

Area of Science:

• Neuroscience
• Genetics
• Metabolic Disorders

Background:

• Creatine transporter deficiency (CTD) is an X-linked intellectual disability (ID) caused by SLC6A8 mutations.
• Limited data exists on the adult progression of CTD, with no prior treatment studies in this demographic.

Observation:

• Two adult half-brothers with CTD presented with progressive symptoms including speech, walking, and feeding difficulties, leading to fatigue and malnutrition.
• Intervention trials were conducted using arginine, glycine, creatine, and betaine supplements.

Findings:

• Betaine supplementation demonstrated significant benefits in both patients, improving balance, speech, feeding, reducing exhaustion, and aiding weight management.
• Arginine and glycine supplementation were associated with adverse effects in one patient.
• Cessation of betaine led to symptom deterioration, with improvement upon re-initiation.

Implications:

• Betaine is a potentially safe and effective treatment for adult CTD patients, offering a novel therapeutic strategy.
• Betaine's mechanism may involve antagonism of NKCC1 channels, similar to bumetanide, which has shown promise in autism and epilepsy.
• Further rigorous studies are warranted to confirm betaine's efficacy in CTD.