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HelpTest ID C4U C4 Acylcarnitine, Quantitative, Random, Urine
Reporting Name
C4 Acylcarnitine, QN, UUseful For
Evaluation of patients with abnormal newborn screens showing elevations of iso-/butyrylcarnitine to aid in the differential diagnosis of short-chain acyl-CoA dehydrogenase and isobutyryl-CoA dehydrogenase deficiencies
Specimen Type
UrineOrdering Guidance
This second-tier test is used specifically to evaluate a newborn screening elevation of iso-/butyrylcarnitine and must not be ordered with either C5OHU / C5-OH Acylcarnitine, Quantitative, Random, Urine or C5DCU / C5-DC Acylcarnitine, Quantitative, Random, Urine.
For general screening for metabolic disorders, see OAU / Organic Acids Screen, Random, Urine; ACRN / Acylcarnitines, Quantitative, Plasma; and AAQP / Amino Acids, Quantitative, Plasma.
Necessary Information
Include patient's age, family history, clinical condition (asymptomatic or acute episode), diet, and drug therapy information.
Specimen Required
Patient Preparation: If clinically feasible, discontinue L-carnitine supplementation at least 72 hours before specimen collection.
Supplies: Urine Tubes, 10 mL (T068)
Collection Container/Tube: Clean, plastic urine collection container
Submission Container/Tube: Plastic, 10 mL urine tube
Specimen Volume: 5 mL
Collection Instructions:
1. Collect a random urine specimen.
2. Freeze specimen immediately.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Urine | Frozen (preferred) | 7 days | |
| Refrigerated | 24 hours |
Reference Values
<3.00 millimoles/mole creatinine
Day(s) Performed
Monday, Wednesday, Friday
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
82017
Genetics Test Information
Elevated iso-/butyrylcarnitine (C4) in plasma or newborn screening blood spots is due to either short chain acyl-CoA dehydrogenase (SCAD) deficiency or isobutyryl-CoA dehydrogenase (IBD) deficiency.
Urine C4 results can distinguish between SCAD deficiency, which results in normal C4 in urine, and IBD deficiency, which results in elevated C4 in urine.
Clinical Information
An isolated elevation of iso-/butyrylcarnitine (C4) in plasma or newborn screening blood spots is related to a diagnosis of either short chain acyl-CoA dehydrogenase (SCAD) deficiency or isobutyryl-CoA dehydrogenase (IBD) deficiency. Diagnostic testing by acylcarnitine analysis, including the evaluation of C4 excretion in urine, is necessary to differentiate the 2 clinical entities.(1) Patients with IBD deficiency excrete an abnormal amount of C4 acylcarnitine in urine, whereas patients with SCAD deficiency can have a normal excretion of this metabolite.
Interpretation
Almost all patients with isobutyryl-CoA dehydrogenase deficiency excrete an abnormal amount of iso-/butyrylcarnitine (C4) in their urine. Some, but not all, affected individuals also excrete elevated levels of isobutyrylglycine. Conversely, patients with short-chain acyl-CoA dehydrogenase deficiency can have a normal excretion of C4.
Cautions
The results of urine acylcarnitines are typically not informative when the patient is receiving L-carnitine supplements.
Clinical Reference
1. Miller MJ, Cusmano-Ozog K, Oglesbee D, Young S; ACMG Laboratory Quality Assurance Committee: Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(2):249-258
2. Oglesbee D, Vockley J, Ensenauer RE, et al. Ten cases of isobutyryl-CoA dehydrogenase (IBDH) deficiency detected by newborn screening. J Inherit Metab Dis. 2005;28(Suppl 1):13. doi: 10.1007/s10545-004-0001-x
3. Oglesbee D, He M, Majumder N, et al. Development of a newborn screening follow-up algorithm for the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genet Med. 2007;9(2):108-116
Method Description
Acylcarnitines, including iso-butyrylcarnitine, are determined in urine by flow injection analysis tandem mass spectrometry using acetyl-d3-carnitine, propionyl-d3-carnitine, butyryl-d3-carnitine, octanoyl-d3-carnitine, dodecanoyl-d3-carnitine, and palmitoyl-d3-carnitine as internal standards. The supernatant is evaporated and the residue treated with n-butanolic hydrochloric acid yielding the acylcarnitines for analysis as their n-butyl esters.(Tortorelli S, Hahn SH, Cowan TM, et al. The urinary excretion of glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric acidemia type I. Mol Genet Metab. 2005;84(2):137-143; Miller MJ, Cusmano-Ozog K, Oglesbee D, Young S; ACMG Laboratory Quality Assurance Committee. Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American College of Medical Genetics and Genomics [ACMG]. Genet Med. 2021;23[2]:249-258)
Report Available
2 to 5 daysReject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.NY State Approved
YesMethod Name
Flow Injection Analysis-Tandem Mass Spectrometry (FIA-MS/MS)
Forms
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
mcl-newborn