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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.
Differential diagnosis between disorders of peroxisomal biogenesis (eg, Zellweger syndrome) and disorders with loss of a single peroxisomal function
Abnormal elevations of pipecolic acid can be detected in either serum or 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, and 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 which increase with age.
Abnormal results may reflect either prematurity or nongenetic liver and/or renal disease.
<6 months: < or =6.0 nmol/mL
6 months-<1 year: < or =5.9 nmol/mL
1-17 years: < or =4.3 nmol/mL
> or =18 years: < or =7.4 nmol/mL
1. Gould SJ, Raymond GV, Valle D: The peroxisome biogenesis disorders. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, D Valle, et al. New York, McGraw-Hill Book Company, 2001, pp 3181-3217
2. Wanders RJA, Barth PG, Heymans HAS: Single peroxisomal enzyme deficiencies. In The Metabolic and Molecular Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, D Valle, et al. New York, McGraw-Hill Book Company, 2001, pp 3247-3248