X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demyelinating disease (cerebral ALD). Hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. Unfortunately, this narrow therapeutic window is often missed. Therefore, an increasing number of newborn screening programs are including ALD. To identify new biomarkers for ALD, we developed an Abcd1 knockout mouse with enhanced VLCFA synthesis either ubiquitous or restricted to oligodendrocytes. Biochemical analysis revealed VLCFA accumulation in different lipid classes and acylcarnitines. Both C26:0-lysoPC and C26:0-carnitine were highly elevated in brain, spinal cord, but also in bloodspots. We extended the analysis to patients and confirmed that C26:0-carnitine is also elevated in bloodspots from ALD patients. We anticipate that validation of C26:0-carnitine for the diagnosis of ALD in newborn bloodspots may lead to a faster inclusion of ALD in newborn screening programs in countries that already screen for other inborn errors of metabolism.

The morphogenetic response of Ligusticum porteri, a medicinal and ceremonial plant, was investigated as part of the conservation strategy of this wild species and was compared to that of a cultivated species, Petroselinum crispum. Seeds were germinated in half strength Murashige and Skoog medium. Plantlets were excised into root, cotyledon, petiole, stem and leaf explants and cultured in an induction medium supplemented with the range of 0-18.09 lM 2,4-dichlorophenoxyacetic acid (2,4-D) or 0-21.48 lM a-naphthaleneacetic acid in combination with 0-13.31 lM 6-benzylaminopurine. Calli derived from leaf, seeds, petiole, stem and roots, mature aerial parts and roots extracts of L. porteri and P. crispum were analyzed by thin layer chromatography and gas chromatography coupled to mass spectrometry. 3-Butylidenephthalide (6.3%) was identified along with other 23 compounds from mature aerial parts extract of L. porteri and also in its roots (20.8%). 3-nButylphthalide (0.7%) and 3,6,7,-trimethoxy-isobenzofuran-13(H)-one (4.9%) were identified from the roots of P. crispum.3-Butylidenephthalide was identified from two petiole (0.9%; 0.26%) and one stem (0.8%) callus extracts of L. porteri. This is the first report on phthalides production from in vitro cultures of L. porteri. The results indicated that in vitro cultures of this plant possess the biosynthetic machinery for the biosynthesis of these highly valuable compounds.

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