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
- D. W. Johnson
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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 (C20:0), docosanoic (C22:0), tetracosanoic (C24:0) and hexacosanoic (C26:0) acids by electrospray tandem mass spectrometry. The C26:0/C22:0 and C24:0/C22:0 ratios are significantly greater in the plasma of patients with peroxisomal disorders compared to controls. The C20:0/C22:0 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 C26:0/C22:0 ratios compared to age-matched controls.
- Aubourg P, Bougneres PF, Rocchiccioli F (1985) Capillary gas-liquid chromatographic-mass spectrometric measurement of very long chain to fatty acids in microlitre samples (C22 C26) of plasma. J Lipid Res 26: 263–267.
- Aveldano MI, Horrocks LA (1983) Quantitative release of fatty acids from lipids by a simple hydrolysis procedure. J Lipid Res 24: 1101–1105.
- Bootsma AH, Overmars H, van Rooj A, et al (1999) Rapid analysis of conjugated bile acids in plasma using electrospray tandem mass spectrometry: application for selective screening of peroxisomal disorders. J Inherit Metab Dis 22: 307–310.
- Harvey DJ (1984) Picolinyl derivatives for the structural determination of fatty acids by mass spectrometry: applications to polyenoic acids, hydroxy acids, di-acids and related compounds. Biomed Mass Spectrom 11: 340–347.
- Inoue K, Suzuki Y, Yajima S, Shimozawa N, Orii T, Kondo N (1997) Very long chain fatty acid analysis of dried blood spots on Ðlter paper to screen for adrenoleukodystrophy. Clin Chem 43: 2197–2198.
- Ishikawa Y, Minami R, Nakao T (1985) Diagnosis of adrenoleukodystrophy using dried blood spots. Tohoku J Exp Med 146: 69–72.
- Jakobs C, van den Heuvel CMM, Stellaard F, Largilliere C, Skovby F, Christensen E (1993) Diagnosis of Zellweger syndrome by analysis of very long-chain fatty acids in stored blood spots collected at neonatal screening. J Inherit Metab Dis 16: 63–66.
- Johnson DW, Stockham P, Beckman K, Paton BC, Poulos A (1995) Probing the metabolism of very long chain fatty acids with deuterated isolignoceric acid. In Allen, J, Vosges R, eds. Applications of Isotopes and Isotopically L abeled Compounds 1994. Amsterdam: Elsevier, 839–842.
- Lazarow PB, Moser HW (1995) Disorder of peroxisome biogenesis. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds: The Metabolic and Molecular Bases of Inherited Disease, 7th edn, vol. 2. New York: McGraw-Hill, 2287–2325.
- Levy HL (1998) Newborn screening by tandem mass spectrometry: a new era. Clin Chem 44: 2401–2402.
- Mills KA, Mushtaq I, Johnson AW, WhitÐeld PD, Clayton PT (1998) A method for the quantitation of conjugated bile acids in dried blood spots using electrospray ionization-mass spectrometry. Pediatr Res 43: 361–368.
- Moser HW, Moser AB (1991) Measurement of saturated very long chain fatty acids in plasma. In Hommes FA, ed. Techniques in Diagnostic Human Biochemical Genetics New York: Wiley Liss, 177–191.
- Moser AB, Borel J, Odone A, et al (1987) A new dietary therapy for adrenoleukodystrophy: biochemical and preliminary clinical results in 36 patients. Ann Neurol 21: 240–249.
- Moser AB, Kreiter N, Bezman L, Lu S, Raymond GV, Naidu S, Moser MW (1999) Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 45: 100–110.
- Nishio H, Kodama S, Yokoyama S, Matsuo T, Mio T, Sumino K (1986) A simple method to diagnose adrenoleukodystrophy using a dried blood spot on filter paper. Clin Chim Acta 159: 77–82.
- Paik MJ, Lee KO, Shin HS (1999) Determination of very-long-chain fatty acids in serum by gas chromatography-nitrogen-phosphorus detection following cyanomethylation. J Chromatogr B Biomed Sci Appl 721: 3–11.
- Schutgens RB, Bouman IW, Nijenhuis AA, Wanders RJ, Frumau ME (1993) Profiles of verylong chain fatty acids in plasma Ðbroblasts, and blood cells in Zellweger syndrome, Xlinked adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata. Clin Chem 39: 1632–1637.
- Stellaard F, ten Brink HJ, Kok RH, van den Heuvel L, Jakobs C (1990) Stable isotope dilution analysis of very long chain fatty acids in plasma, urine and amniotic Ñuid by electron capture negative ion mass fragmentography. Clin Chim Acta 192: 133–144.
- Sweetman L (1996) Newborn screening by tandem mass spectrometry (MS-MS). Clin Chem 42: 345–346.
- Ten Brink HJ, Schor DS, Kok RM, Poll-The BT, Wanders RJA, Jakobs C (1992) Phytanic acid a-oxidation: accumulation of 2-hydroxyphytanic acid and absence of 2-oxophytanic acid in plasma from patients with peroxisomal disorders. J Lipid Res 33: 1449–1457.
- Vallance H, Applegarth D (1994) An improved method for quantiÐcation of very long chain fatty acids in plasma. Clin Biochem 27: 183–186.
- 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
Journal of Inherited Metabolic Disease
Volume 23, Issue 5 , pp 475-486
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- Kluwer Academic Publishers
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- D. W. Johnson (1)
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- 1. Department of Chemical Pathology, Women's and Children's Hospital, 72 King William Rd, North Adelaide, South Australia, 5006, Australia