For the diagnosis of peroxisomal disorders and pyridoxine-dependent epilepsy.
The essential amino acid lysine can be degraded via two pathways, the saccharopine pathway and the pipecolic acid (PA) pathway. Both pathways merge at the level of α-aminoadipic acid semialdehyde (AASA). It is generally accepted that the saccharopine pathway constitutes the major breakdown pathway. However, the PA pathway has attracted much attention since the discovery of the association between the presence of elevated PA levels and Zellweger syndrome almost 40 years ago. Mainly because the analysis of amino acids was the primary biochemical approach for studying presumed inborn errors of metabolism, PA in Zellweger syndrome was discovered even before it was realized that this disorder was based on a defect of peroxisomal functions.
The clinical importance of PA remained limited for a long time until it was realized that this amino acid was elevated in all patients with so-called pyridoxine-responsive convulsions (4 to 15 – fold in plasma). Following the discovery of a genetic defect of AASA dehydrogenase as the underlying cause of this disorder – leading to a secondary increase of PA – the analysis of this amino acid again became an important diagnostic tool.
Pipecolic acidemia, also called hyperpipecolic acidemia or hyperpipecolatemia, is a very rare autosomal recessive metabolic disorder that is caused by a peroxisomal defect.
Pipecolic acidemia can also be an associated component of Refsum disease with increased pipecolic acidemia (RDPA), as well as other peroxisomal disorders, including both infantile and adult Refsum disease, and Zellweger syndrome.
Plasma:Urine (>6mths): 0.01 – 1.54 umol/mmol creat
Urine (<6mths): 0.6 – 24.0 umol/mmol creat
Plasma: Lithium Heparin or EDTA
Urine: Random urine in Plain Container.
If patient taking pyridoxine prior to sample being taken clarify by taking a CSF Pipecolic sample (Sheffield – 0114 2717340) or urine alpha-aminoadipyl semialdehyde (Prof. P Clayton, Institute Child Health, London – 0207 2429789).
Sheffield Children’s Hospital