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Test ID CRDPU Creatine Disorders Panel, Random, Urine

Reporting Name

Creatine Disorders Panel, U

Useful For

Evaluating patients with a clinical suspicion of arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency, and creatine transporter deficiency

Additional Tests

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

Testing Algorithm

This is a single test that carries the results for the panel. When the test has been 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 Screen Follow-up for Guanidinoacetate Methyltransferase Deficiency (GAMT)

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

 

If the patient has abnormal newborn screening results for guanidinoacetate methyltransferase deficiency, refer to the appropriate ACMG Newborn Screening ACT Sheet.(1)

Specimen Type

Urine


Necessary Information


Patient's age and sex are required.



Specimen 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.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Urine Frozen 29 days

Reference Values

Males

Age

Creatinine (nmol/mL)

Guanidinoacetate (nmol/mL)

Creatine (nmol/mL)

Creatine/
creatinine

≤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

≤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

Day(s) Performed

Tuesday

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

82540

82570

82542

Disease States

  • CrT1 defect
  • Creatine transporter (SLC6A8) deficiency

Clinical Information

Disorders of creatine synthesis (guanidinoacetate methyltransferase [GAMT] deficiency, L-arginine:glycine amidinotransferases [AGAT] deficiency, and creatine transporter deficiency [CTD]) 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 especially expressive speech and language delay and intellectual disability. Affected patients may have abnormal magnetic resonance imaging findings and exhibit cerebral creatine deficiency in brain magnetic resonance spectroscopy. Patients with GAMT and male patients with CTD may develop seizures, autistic-like behaviors, and abnormal movements. Female carriers for CTD can be asymptomatic or exhibit features similar to affected male patients, such as intellectual disability, behavioral problems, and 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. The only consistently reliable method for diagnosis of CTD in female patients is molecular analysis of the SLC6A8 gene. The diagnosis of GAMT, AGAT, and CTD can be confirmed by molecular analysis of GAMT,GATM, and SLC6A8 respectively.

 

Treatment with oral supplementation of creatine monohydrate is available and effective for the AGAT and GAMT deficiencies. Patients with GAMT deficiency may also be treated with supplemental ornithine and dietary arginine restriction. CTD is treated with oral creatine monohydrate and arginine and glycine supplementation.

 

Early treatment has been reported to prevent disease manifestations in affected but presymptomatic newborn siblings of individuals with GAMT or AGAT deficiencies.

Interpretation

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.

Cautions

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

 

Creatine supplementation will cause falsely elevated results.

Clinical Reference

1. ACMG Newborn Screening ACT Sheets. Accessed December 16, 2024. Available at www.acmg.net/ACMG/Medical-Genetics-Practice-Resources/ACT_Sheets_and_Algorithms/ACMG/Medical-Genetics-Practice-Resources/ACT_Sheets_and_Algorithms.aspx?hkey=9d6bce5a-182e-42a6-84a5-b2d88240c508

2. Clark JF, Cecil KM. Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes. Pediatr Res. 2015;77(3):398-405

3. Mercimek-Mahmutoglu S, Salomons GS. Creatine deficiency syndromes. In: Adam MP, Mirzaa GM, Pagon RA, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2009. Updated February 10, 2022. Accessed December 16, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK3794/

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

5. Longo N, Ardon O, Vanzo R, Schwartz E, Pasquali M. Disorders of creatine transport and metabolism. Am J Med Genet. 2011;157:72-78. doi:10.1002/ajmg.c.30292

6. Bahl S, Cordeiro D, MacNeil L, Schulze A, Mercimek-Andrews S. Urine creatine metabolite panel as a screening test in neurodevelopmental disorders. Orphanet J Rare Dis. 2020;15(1):339. doi:10.1186/s13023-020-01617-z

7. Fernandes-Pires G, Braissant O. Current and potential new treatment strategies for creatine deficiency syndromes. Mol Genet Metab. 2022;135(1):15-26. doi:10.1016/j.ymgme.2021.12.005

Method Description

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 liquid chromatography tandem mass spectrometry system with Analyst software.(Bodamer OA, Bloesch SM, Gregg AR, Stockler-Ipsiroglue S, O'Brien WEO. Analysis of guanidinoacetate and creatine by isotope dilution electroscopy tandem mass spectrometry. Clin Chim Acta. 2001;308:173-178; Cognat S, Cheillan D, Piraud M, Roos B, Jakobs C, Vianey-Saban C. Determination of guanidinoacetate and creatine in urine and plasma by liquid chromatography-tandem mass spectrometry. Clin Chem. 2004;50[8]:1459-1461)

Report Available

3 to 9 days

Reject Due To

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

NY State Approved

Yes

Method Name

Liquid Chromatography Tandem Mass Spectometry (LC-MS/MS)

Genetics Test Information

Depletion of cerebral creatine occurs in all 3 types of creatine deficiency syndromes (CDS): arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency, and creatine transporter deficiency.

 

Measurement of guanidinoacetate, creatine (Cr), and creatinine (Crn) in urine, along with the Cr:Crn ratio, aids in distinguishing the types of creatine deficiency syndromes.

 

Treatment with oral creatine supplementation is effective in some types of CDS.

 

Creatine supplementation may impact reliability of test results.

Mayo Clinic Laboratories | Pediatric Catalog Additional Information:

mcl-newborn