A rapid screening procedure for the diagnosis of peroxisomal disorders: Quantification of very long‐chain fatty acids, as dimethylaminoethyl esters, in plasma and blood spots, by electrospray tandem mass spectrometry

Abstract

A rapid method with potential to screen for many of the peroxisomal disorders using 5μl of plasma or a 3‐mm blood spot (3.6μl blood impregnated on filter paper) is described. Fatty acids are liberated from plasma or blood spots and converted to dimethylaminoethyl esters. Trideuterated fatty acids, added as internal standards, are used to quantify eicosanoic (C_20:0), docosanoic (C_22:0), tetracosanoic (C_24:0) and hexacosanoic (C_26:0) acids by electrospray tandem mass spectrometry. The C_26:0/C_22:0 and C_24:0/C_22:0 ratios are significantly greater in the plasma of patients with peroxisomal disorders compared to controls. The C_20:0/C_22:0 ratio is elevated in the plasma of peroxisomal patients who accumulate phytanic acid. Blood spots collected from four peroxisomal patients between 2 and 10 days after birth and stored for up to 17 years, were shown to give between 33% and 233% higher C_26:0/C_22:0 ratios compared to age‐matched controls.