Table 1.

Specialized Biochemical Testing in PBD, ZSS

CompoundTest Expected FindingsLimitations of Test
Very-long-chain fatty acids (VLCFA)Plasma concentrationElevated plasma concentrations of C26:0 and C26:1; elevated ratios of C24/C22 and C26/C22 1 Non-fasting samples, hemolyzed samples, or an individual on a ketogenic diet can cause false-positive results. Normal in RCDP.
Phytanic acid and pristanic acid 2 Plasma concentrationIncreased concentrations of phytanic acid and/or pristanic acid Branched-chain fatty acid accumulation occurs only through dietary intake of phytanic acid. Thus, phytanic and pristanic acid levels are normal in a neonate with a PBD.
PlasmalogensErythrocyte membrane concentrationsProfoundly diminished concentration of C16 and C18 plasmalogens (possible)Concentration of erythrocyte plasmalogens may improve with age. Not all newborns with PBD have reduced levels.
Pipecolic acidPlasma/urine concentrationIncreased concentration of pipecolic acid in both plasma and urineUrinary excretion of pipecolic acid is high in the neonatal period and diminishes with age. 3
Bile acidsPlasma/urine concentrationAccumulation of intermediates THCA and DHCASome defects may be subtle.

DHCA = dihydroxycholestanoic acid

THCA = trihydroxycholestanoic acid

1. Low plasma concentration of LDL and HDL can cause false-negative results. In a person with low plasma concentrations of LDL and HDL without a defect in peroxisomal fatty acid metabolism, the plasma concentration of specific fatty acids (C22:0, C24:0, C26:0, etc) are significantly lower than normal control levels. Individuals with defects in peroxisomal fatty acid metabolism and very low LDL and HDL concentrations do not have significant elevations in C26:0 and C26:1, but do have modest elevations in the ratios of C24/C22 and C26/C22.

2. This analysis is usually included in VLCFA measurement.

3. Pipecolic acid measurement is an adjunct to more definitive biomarkers such as plasma VLCFA and erythrocyte plasmalogen levels. Elevations in pipecolic acid can occur in pyridoxine-dependent seizures [Plecko et al 2000] and in individuals with psychomotor retardation who have normal levels of other peroxisomal metabolites [Baas et al 2002]. Thus, isolated elevation of plasma concentration of pipecolic acid is not necessarily indicative of a primary defect in peroxisomal metabolism.

From: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum

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