Cerebral creatine deficiency

Cerebral Creatine Deficiency Syndrome

Cerebral Creatine Deficiency Syndrome (CCDS) is a group of inherited metabolic disorders that affect the brain's ability to synthesize or transport creatine. Creatine is crucial for energy storage and supply in the brain and muscles. CCDS is characterized by developmental delays, intellectual disabilities, and seizures.

Types of Cerebral Creatine Deficiency

CCDS is classified into three main types based on the specific genetic mutation involved:

• Guanidinoacetate Methyltransferase Deficiency (GAMT): This type is caused by mutations in the GAMT gene, leading to a deficiency in the enzyme guanidinoacetate methyltransferase, which is necessary for the conversion of guanidinoacetate to creatine.

• Arginine:Glycine Amidinotransferase Deficiency (AGAT): This type results from mutations in the GATM gene, affecting the enzyme arginine:glycine amidinotransferase, which is involved in the first step of creatine synthesis.

• Creatine Transporter Deficiency (CTD): This type is due to mutations in the SLC6A8 gene, which encodes the creatine transporter protein responsible for transporting creatine into the brain.

Symptoms

The symptoms of CCDS can vary depending on the type and severity of the disorder, but common symptoms include:

• Developmental delay
• Intellectual disability
• Speech delay
• Seizures
• Behavioral problems

Diagnosis

Diagnosis of CCDS typically involves a combination of clinical evaluation, biochemical tests, and genetic testing. Key diagnostic tests include:

• Measurement of creatine and guanidinoacetate levels in urine, blood, and cerebrospinal fluid.
• Magnetic resonance spectroscopy (MRS) to detect creatine levels in the brain.
• Genetic testing to identify mutations in the GAMT, GATM, or SLC6A8 genes.

Treatment

Treatment strategies for CCDS depend on the specific type of deficiency:

• For GAMT deficiency, treatment may include creatine supplementation, dietary restriction of arginine, and supplementation with ornithine.
• For AGAT deficiency, creatine supplementation is the primary treatment.
• For CTD, treatment options are limited, but creatine supplementation may be attempted, although it is often ineffective due to the transport defect.

Prognosis

The prognosis for individuals with CCDS varies. Early diagnosis and treatment can improve outcomes, particularly for GAMT and AGAT deficiencies. However, CTD often has a more challenging prognosis due to the lack of effective treatments.

Research and Future Directions

Ongoing research aims to better understand the pathophysiology of CCDS and develop more effective treatments. Gene therapy and other novel approaches are being explored as potential future therapies.

NIH genetic and rare disease info

• NIH info on Cerebral creatine deficiency

Cerebral creatine deficiency is a rare disease.