Differentiating between disorders of peroxisomal biogenesis (eg, Zellweger syndrome) and disorders with loss of a single peroxisomal function
Detecting abnormal elevations of pipecolic acid in urine
Pipecolic acid is not detected by conventional organic acid analysis of urine.
In the newborn period, pipecolic acid levels are more likely to be abnormal in urine than in plasma or serum. Abnormal levels of pipecolic acid should be interpreted together with the results of other biochemical markers of peroxisomal disorders, such as plasma C22-C26 very long-chain fatty acids, phytanic acid, pristanic acid, RBC plasmalogens, and bile acid intermediates.
Measurement of pipecolic acid is a useful diagnostic tool for differentiating between peroxisomal biogenesis disorders (Zellweger spectrum disorders) and peroxisomal disorders caused by single enzyme deficiencies such as X-linked adrenoleukodystrophy.
Results must be interpreted together with the results of other biochemical markers for peroxisomal disorders.
Both urine and plasma are suitable specimens for the detection of pipecolic acid.
See Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm in Special Instruction.
Gas Chromatography-Mass Spectrometry (GC-MS)
See Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm in Special Instruction.
Urine
Patient's age is required.
Supplies: Plastic, 10-mL urine tube (T068)
Container/Tube: Plastic, 10-mL urine tube
Specimen Volume: 5 mL
Collection Instructions:
1. Collect a random urine specimen.
2. No preservative.
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
2 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Urine | Frozen (preferred) | 94 days | |
Refrigerated | 14 days |
Differentiating between disorders of peroxisomal biogenesis (eg, Zellweger syndrome) and disorders with loss of a single peroxisomal function
Detecting abnormal elevations of pipecolic acid in urine
Pipecolic acid is not detected by conventional organic acid analysis of urine.
In the newborn period, pipecolic acid levels are more likely to be abnormal in urine than in plasma or serum. Abnormal levels of pipecolic acid should be interpreted together with the results of other biochemical markers of peroxisomal disorders, such as plasma C22-C26 very long-chain fatty acids, phytanic acid, pristanic acid, RBC plasmalogens, and bile acid intermediates.
See Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm in Special Instruction.
Increased pipecolic acid levels may also be seen in alpha-aminoadipic semialdehyde dehydrogenase deficiency (pyridoxine dependent epilepsy), hyperlysinemia types 1 and 2, and defects in proline metabolism.
Theoretically, a defect in L-pipecolate oxidase can exist and several cases of hyperpipecolic acidemia have been reported, but a specific enzyme deficiency has not been described in any of the patients.
< or =31 days: < or =223.8 nmol/mg creatinine
32 days-5 months: < or =123.1 nmol/mg creatinine
6 months-11 months: < or =45.0 nmol/mg creatinine
> or =1 year: < or =5.7 nmol/mg creatinine
Elevated pipecolic acid levels are seen in disorders of peroxisomal biogenesis; normal levels are seen in disorders with loss of a single peroxisomal function.
Abnormal levels of pipecolic acid should be interpreted together with the results of other biochemical markers of peroxisomal disorders, such as serum C22-C26 very long-chain fatty acids, phytanic acid, pristanic acid (POX / Fatty Acid Profile, Peroxisomal [C22-C26], Serum); red blood cell plasmalogens; and bile acid intermediates.
Newborns with disorders of peroxisomal biogenesis often have normal levels of pipecolic acid that increase with age.
Abnormal results may reflect either prematurity or nongenetic liver and/or renal disease.
Pipecolic acid is not detected by conventional organic acid analysis (OAU / Organic Acids Screen, Random, Urine).
Vigabatrin interferes with pipecolic acid determination.
Methylmalonic acid interferes with pipecolic acid determination.
1. Gartner J, Rosewich H, Thoms S. The peroxisome biogenesis disorders. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw Hill; 2019. Accessed July 16, 2021. Available at www.ommbid.com
2. Wanders RA, Barth PG, Heymans HA. Single peroxisomal enzyme deficiencies. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw Hill; 2019. Accessed July 16, 2021. Available at www.ommbid.com
3. Peduto A, Baumgartner MR, Verhoeven NM, et al: Hyperpipecolic acidaemia: a diagnostic tool for peroxisomal disorders. Mol Genet Metab. 2004;82:224-230
4. Braverman N, Raymond G, Rizzo WB, et al: Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar;117(3):313-321
Pipecolic acid is quantitated by a stable isotope dilution method; electron capture negative chemical ionization gas chromatography-mass spectrophotometry of pentafluorobenzyl esters.(Kok RM, Kaster L, de Jong AP, et al: Stable isotope dilution analysis of pipecolic acid in cerebrospinal fluid, plasma, urine and amniotic fluid using electron capture negative ion mass fragmentography. Clin Chim Acta. 1987;168:143-152, Kuhara t, Akiyama T, Ohse M, et al: Identification of new biomarkers of pyridoxine-dependent epilepsy by GC/MS-based urine metabolomics. Anal Biochem. 2020 Sep 1;604:113739. doi: 10.1016/j.ab.2020.113739)
Thursday
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.
82542
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
PIPU | Pipecolic Acid, U | 33659-4 |
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.
|
---|---|---|
81248 | Pipecolic Acid, U | 33659-4 |
29952 | Interpretation | 59462-2 |
29954 | Reviewed By | 18771-6 |