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Pipecolic acid (PA) is an intermediate of lysine metabolism and is oxidized in the peroxisomes by the enzyme L-pipecolate oxidase. In peroxisome biogenesis disorders (eg, Zellweger syndrome), the activity of this enzyme is lost, resulting in an increase in pipecolic acid levels. In contrast, in peroxisomal disorders involving single enzyme deficiencies such as D-bifunctional protein deficiency, PA is not elevated; therefore PA analysis is useful for differentiating between these 2 groups of disorders.
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.
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
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 plasma C22-C26 very long-chain fatty acids, phytanic acid, pristanic acid (POX / Fatty Acid Profile, Peroxisomal [C22-C26], Serum), RBC 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, Urine).
Vigabatrin interferes with pipecolic acid determination.
Methylmalonic acid interferes with pipecolic acid determination.
< 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
1. Gould SJ, Raymond GV, Valle D: Chapter 129: The peroxisome biogenesis disorders. In Scriver's Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill Education. Accessed 03/16/15. Available at www.ommbid.com
2. Wanders RJA, Barth PG, Heymans HAS: Chapter 130: Single peroxisomal enzyme deficiencies. In Scriver's Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill Education. Accessed 03/16/15. 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