Test ID: CRDPU    
Creatine Disorders Panel, Urine

Evaluation of patients with a clinical suspicion of inborn errors of creatine metabolism including arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency, and creatine transporter (SLC6A8) defect

Disorders of creatine synthesis (deficiency of arginine:glycine amidinotransferase [AGAT] and guanidinoacetate methyltransferase [GAMT]) and the creatine transporter (SLC6A8) deficiency are collectively described as creatine deficiency syndromes (CDS). AGAT and GAMT deficiencies are inherited in an autosomal recessive manner, while the creatine transporter defect is X-linked. All 3 disorders result in a depletion of cerebral creatine and typically present with cognitive disability, speech and language delays, and seizures. Patients with GAMT and the creatine transporter deficiency exhibit behavioral problems and features of autism. Some female carriers for the creatine transporter deficiency have been reported with learning disabilities and behavioral problems.

Diagnosis is possible by measuring guanidinoacetate (GAA), creatine (Cr), and creatinine (Crn) in plasma and urine. The profiles are specific for each clinical entity. Patients with GAMT deficiency typically exhibit normal to low Cr, very elevated GAA, and low Crn. In patients with AGAT deficiency, normal to low Cr, low GAA, and normal to low Crn is observed. In comparison, elevated Cr, normal GAA, normal to low Crn, and an elevated Cr:Crn ratio characterize patients with creatine transporter defect.

Treatment with oral supplementation of creatine monohydrate is available and effective for the AGAT and GAMT deficiencies; it has not been shown to improve outcomes in individuals with the creatine transporter defect.

Males

Females

Reports include concentrations of guanidinoacetate, creatine, and creatinine, and a calculated creatine:creatinine ratio. When no significant abnormalities are detected, a simple descriptive interpretation is provided. When abnormal results are detected, a detailed interpretation is given. This interpretation includes an overview of the results and their significance, a correlation to available clinical information, elements of differential diagnosis, and recommendations for additional biochemical testing.

Correct specimen collection and handling is crucial to achieve reliable results.

Creatine supplementation will cause falsely elevated results.

1. Sykut-Cegielska J, Gradowska W, Mercimek-Mahutoglu S, Stockler-Ipsiroglu S: Biochemical and clinical characteristics of creatine deficiency syndromes. Acta Biochim Pol 2004;51:875-882

2. Stromberger C, Bodamer OA, Stockler-Ipsiroglu S: Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism. J Inherit Metab Dis 2003;26:299-308

3. Stockler S, Schultz PW, Salomons GS: Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology. Subcell Biochem 2007;46:149-166

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