Creatine Disorders Panel Testing

Creatine deficiency syndromes include guanidinoacetate methyltransferase (GAMT) deficiency, L-arginine:glycine amidinotransferase (AGAT) deficiency, and creatine transporter deficiency. GAMT deficiency and AGAT deficiency are related to creatine biosynthesis, while creatine transporter deficiency is related to creatine transport. All three disorders are characterized by intellectual disability, seizure disorder (variable severity), developmental delay, speech/language delay, movement disorder, and behavioral disorder (autism, hyperactivity, self-injury). Disease onset is generally observed in early childhood. Diagnosis often includes magnetic resonance (MR) spectroscopy, biochemical testing, and genetic testing. Biochemical testing should include measurement of guanidinoacetate (GAA) and creatine in urine and plasma, and evaluation of the creatine:creatinine ratio in urine.

Disease Information

Creatine deficiency syndromes are relatively rare and associated with genetic variance in the GATM, GAMT, and SLC6A8 genes. The table below details gene associations, inheritance patterns, and incidence for AGAT, GAMT, and creatine transporter deficiency syndromes.

Results

The table below details the expected biochemical results for AGAT, GAMT, and creatine transporter deficiency syndromes. Clinical correlation is necessary for complete evaluation of laboratory results.

In addition to GAMT deficiency, elevated GAA can be observed secondary to dietary supplements or in other conditions such as urea cycle disorders. Reevaluation of plasma creatine and guanidinoacetate, and evaluation of plasma amino acid should be performed to exclude a disorder of creatine biosynthesis.