Comparison of C26:0-carnitine and C26:0-lysophosphatidylcholine as diagnostic markers in dried blood spots from newborns and patients with adrenoleukodystrophy

Abstract X-linked adrenoleukodystrophy(ALD) is the most common leukodystrophywith a birth incidence of 1:14,700 live births. The disease is caused by mutations in ABCD1 and characterized by very long-chain fatty acids(VLCFA) accumulation. In childhood, male patients are at high-risk to develop adrenal insufficiencyand/or cerebral demyelination. Timely diagnosis is essential. Untreated adrenal insufficiencycan be life-threatening and hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. For this reason, ALD is being added to an increasing number of newborn screeningprograms. ALD newborn screeninginvolves the quantification of C26:0-lysoPC in dried blood spotswhich requires a dedicated method. C26:0- carnitine, that was recently identified as a potential new biomarker for ALD, has the advantage that it can be added as one more analyte to the routine analysis of amino acids and acylcarnitines already in use. The first objective of this study was a comparison of the sensitivity of C26:0- carnitineand C26:0-lysoPC in dried blood spotsfrom control and ALD newborns both in a case-control study and in newborns included in the New York State screening program. While C26:0-lysoPC was elevated in all ALD newborns, C26:0- carnitinewas elevated only in 83%. Therefore, C26:0- carnitineis not a suitable biomarker to use in ALD newborn screen. In women with ALD, plasma VLCFA analysis results in a false negative result in approximately 15–20% of cases. The second objective of this study was to compare plasma VLCFA analysis with C26:0- carnitineand C26:0-lysoPC in dried blood spotsof women with ALD. Our results show that C26:0-lysoPC was elevated in dried blood spotsfrom all women with ALD, including from those with normal plasma C26:0 levels. This shows that C26:0-lysoPC is a better and more accurate biomarker for ALD than plasma VLCFA levels. We recommend that C26:0-lysoPC be added to the routine biochemical array of diagnostic tests for peroxisomal disorders.