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
Depletion of cerebral creatine occurs in all 3 types of creatine deficiency syndromes (CDS): arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency, and creatine transporter (SLC6A8) deficiency.
Measurement of guanidinoacetate, creatine (Cr), and creatinine (Crn) in urine along with the Cr:Crn ratio distinguishes among the types of creatine deficiency syndromes.
Treatment with oral creatine supplementation is effective in some types of CDS.
Creatine supplementation may cause increased creatine values.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
CRBO | Creatine, (Bill Only), U | No | Yes |
CRNBO | Creatinine, (Bill Only), U | No | Yes |
GAABO | Guanidinoacetate, (Bill Only), U | No | Yes |
CRDPU / Creatine Disorders Panel, Random, Urine is a single test that carries the results for the panel. When the test is resulted, the following procedures are billed:
-CRBO / Creatine, Urine (Bill Only)
-CRNBO / Creatinine, Urine (Bill Only)
-GAABO / Guanidinoacetate, Urine (Bill Only)
For more information, see Newborn Screening Act Sheet Guanidinoacetate Methyltransferase Deficiency: Increased Guanidinoacetate
The following algorithms are available:
-Newborn Screen Follow-up for Guanidinoacetate Methyltransferase Deficiency (GAMT)
-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm
Liquid Chromatography-Tandem Mass Spectometry (LC-MS/MS)
AGAT (Arginine:Glycine Amidinotransferase) Deficiency
Arginine:Glycine Amidinotransferase Deficiency (AGAT)
CrT1 defect
GAMT (Guanidinoacetate Methyltransferase) Deficiency
Guanidinoacetate Methyltransferase (GAMT) Deficiency
Guanidinoacetate
Guanidinoacetic acid
Creatine urine
Creatinine urine
Creatine/creatinine ratio urine
Creatine disorders
CRDPU / Creatine Disorders Panel, Random, Urine is a single test that carries the results for the panel. When the test is resulted, the following procedures are billed:
-CRBO / Creatine, Urine (Bill Only)
-CRNBO / Creatinine, Urine (Bill Only)
-GAABO / Guanidinoacetate, Urine (Bill Only)
For more information, see Newborn Screening Act Sheet Guanidinoacetate Methyltransferase Deficiency: Increased Guanidinoacetate
The following algorithms are available:
-Newborn Screen Follow-up for Guanidinoacetate Methyltransferase Deficiency (GAMT)
-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm
Urine
Patient's age and sex are required.
Supplies: Urine Tubes, 10 mL (T068)
Container/Tube: Plastic, 10 mL urine tube
Specimen Volume: 1 mL
Collection Instructions:
1. Collect a random urine specimen.
2. Immediately freeze urine specimen.
3. If possible, do not send other tests ordered on same vial of urine. In doing so, the other tests may have increased turnaround time due to the strict frozen criteria of this assay.
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
0.5 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Urine | Frozen | 29 days |
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
Depletion of cerebral creatine occurs in all 3 types of creatine deficiency syndromes (CDS): arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency, and creatine transporter (SLC6A8) deficiency.
Measurement of guanidinoacetate, creatine (Cr), and creatinine (Crn) in urine along with the Cr:Crn ratio distinguishes among the types of creatine deficiency syndromes.
Treatment with oral creatine supplementation is effective in some types of CDS.
Creatine supplementation may cause increased creatine values.
CRDPU / Creatine Disorders Panel, Random, Urine is a single test that carries the results for the panel. When the test is resulted, the following procedures are billed:
-CRBO / Creatine, Urine (Bill Only)
-CRNBO / Creatinine, Urine (Bill Only)
-GAABO / Guanidinoacetate, Urine (Bill Only)
For more information, see Newborn Screening Act Sheet Guanidinoacetate Methyltransferase Deficiency: Increased Guanidinoacetate
The following algorithms are available:
-Newborn Screen Follow-up for Guanidinoacetate Methyltransferase Deficiency (GAMT)
-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm
Disorders of creatine synthesis, deficiency of arginine:glycine amidinotransferases (AGAT), guanidinoacetate methyltransferase (GAMT) deficiency, and 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 global developmental delays, intellectual disability, and severe speech delay. Commonly, patients with CDS develop seizures. Patients with GAMT and the creatine transporter deficiency exhibit behavioral problems and features of autism. Female carriers for the creatine transporter deficiency can have intellectual disabilities and behavioral problems, and some develop seizures.
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. Patients with AGAT deficiency typically exhibit normal to low Cr, low GAA, and normal to low Crn. 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. Early treatment has been reported to prevent disease manifestations in affected but presymptomatic newborn siblings of individuals with GAMT or AGAT deficiencies. Creatine supplementation has not been shown to improve outcomes in male patients with the creatine transporter defect. However, symptomatic female carriers of creatine transporter deficiency have been reported to benefit from creatine supplementation.
Males
Age | Creatinine (nmol/mL) | Guanidinoacetate (nmol/mL) | Creatine (nmol/mL) | Creatine/ creatinine |
< or =31 days | 430-5,240 | 9-210 | 12-2,930 | 0.02-0.93 |
32 days-23 months | 313-9,040 | 16-860 | 18-10,490 | 0.02-2.49 |
2-4 years | 1,140-12,820 | 90-1,260 | 200-9,210 | 0.04-1.75 |
5-18 years | 1,190-25,270 | 40-1,190 | 60-9,530 | 0.01-0.96 |
>18 years (male) | 3,854-23,340 | 30-710 | 7-470 | 0.00-0.04 |
Females
Age | Creatinine (nmol/mL) | Guanidinoacetate (nmol/mL) | Creatine (nmol/mL) | Creatine/ creatinine |
< or =31 days | 430-5,240 | 9-210 | 12-2,930 | 0.02-0.93 |
32 days-23 months | 313-9,040 | 16-860 | 18-10,490 | 0.02-2.49 |
2-4 years | 1,140-12,820 | 90-1,260 | 200-9,210 | 0.04-1.75 |
5-18 years | 1,190-25,270 | 40-1,190 | 60-9,530 | 0.01-0.96 |
>18 years | 1,540-18,050 | 30-760 | 5-2810 | 0.00-0.46 |
Reports include concentrations of guanidinoacetate, creatine, and creatinine, as well as 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 are crucial to achieve reliable results.
Creatine supplementation will cause falsely elevated results.
1. Clark JF, Cecil KM: Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes. Pediatr Res. 2015 Mar;77(3):398-405. doi: 10.1038/pr.2014.203
2. Mercimek-Mahmutoglu S, Salomons GS: Creatine deficiency syndromes. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2009. Updated February 10, 2022. Accessed June 3, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK3794/
3. Stockler S, Schultz PW, Salomons GS: Cerebral creatine deficiency syndromes: Clinical aspects, treatment and pathophysiology. Subcell Biochem. 2007;46:149-166. doi: 10.1007/978-1-4020-6486-9_8
4. Longo N, Ardon O, Vanzo R, et al: Disorders of creatine transport and metabolism. Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):72-78. doi: 10.1002/ajmg.c.30292
A random urine sample is combined with stable isotope-labeled internal standards and acetonitrile. After centrifugation, an aliquot of this diluted sample is analyzed by injection onto liquid chromatography columns that separate the analytes from the bulk of the stable isotope dilution in the positive electrospray selected reaction monitoring mode using the Applied Biosystems API 3200 LC-MC/MC System with Analyst Software.(Bodamer OA, Bloesch SM, Gregg AR, et al: Analysis of guanidinoacetate and creatine by isotope dilution electroscopy tandem mass spectrometry. Clin Chim Acta. 2001 Jun;308(1-2):173-178. doi: 10.1016/s0009-8981(01)00480-6; Cognat S, Cheillan D, Piraud M, et al: Determination of guanidinoacetate and creatine in urine and plasma by liquid chromatography-tandem mass spectrometry. Clin Chem. 2004 Aug;50(8):1459-1461. doi: 10.1373/clinchem.2004.034538)
Tuesday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
82540
82570
82542
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CRDPU | Creatine Disorders Panel, U | 79290-3 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
23383 | Creatine | 15046-6 |
23384 | Creatinine | 14683-7 |
23385 | Guanidinoacetate | 97148-1 |
23268 | Creatine/Creatinine Ratio | 34275-8 |
23270 | Creatine Disorders Panel Interp | 79292-9 |
23272 | Reviewed By | 18771-6 |