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

Huffnagel, Irene C.; Beek, Malu-Clair van de; Showers, Amanda; Orsini, Joseph J.; Klouwer, Femke C. C.; Dijkstra, Inge M. E.; Schielen, Peter C. J. I.; Lenthe, Henk van; Wanders, Ronald J. A.; Vaz, Frédéric M.; Morrissey, Mark A.; Engelen, Marc; Kemp, Stephan

doi:10.1016/j.ymgme.2017.10.012

Cited by 52 publications

(58 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…with a very-long-chain (VLCFAs; >20 C), which cannot be oxidized by mitochondria, or with an odd chain, generated from dietary phytanic acid metabolism (18), and (ii) C24 BAs conjugated with glycine (glyco-BA) or taurine (tauro-BA) (19,26). In parallel, plasma samples were also analyzed by a certified laboratory for established biomarkers in inherited peroxisomal disorders, specifically C26:0-lysophosphatidylcholine (LPC 26:0) (27,28) and the BA intermediates di-and trihydroxycholestanoic (DHCA and THCA) (29).…”

Section: Resultsmentioning

confidence: 99%

“…39) and ACOX1 deficiency (40). In the latter conditions, there are, however, additional major metabolic changes, which were not observed in H-Lrpprc -/mice or in LSFC patients, which include higher circulating levels of LPC 26:0, which is considered a more sensitive marker than AC26:0 of primary peroxisomal disorders (27,28). Second, regarding BA metabolism, although levels of commonly used peroxisomal markers THCA and DHCA were undetectable, changes in C24-conjugated BAs (lower in LSFC patients and H-Lrpprc -/mice) suggest a lower rate of conjugation of BAs (41,42).…”

Section: Discussionmentioning

confidence: 99%

“…This method enables a global analysis of ACs, albeit it was found not to be ideally suited for VLCAC analysis. Hence, we developed a specific semiquantitative method for VLCACs, which also includes LPC 26:0, given the reported correlation between AC26:0 and LPC 26:0 in peroxisomal disorders (27,28).…”

Section: Sample Processing and Analysis By Lc-msmentioning

confidence: 99%

See 2 more Smart Citations

Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder

Ruiz¹,

Cuillerier²,

Daneault³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder

Ruiz¹,

Cuillerier²,

Daneault³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

“…AMN was proposed due to the involvement of a slowly progressive paraparesis, adrenal insufficiency, hypogonadism combined with peripheral nerves neuropathy and sphincter disturbances 4 . With the discovery and application of VLCFA, AMN was soon found to be a form of phenotypic X-ALD 17,18 .…”

Section: Discussionmentioning

confidence: 99%

Clinical, Neuroimaging, Biochemical, and Genetic Features in Six Chinese Patients with Adrenomyeloneuropathy

Wang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention.This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison's disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.

show abstract

“…C26:0‐lysophophatidylcholine was analyzed in differentiated macrophages following the protocol for dried blood spots as described previously 30 …”

Section: Methodsmentioning

confidence: 99%

Vorinostat in the acute neuroinflammatory form of X‐linked adrenoleukodystrophy

Zierfuss

Weinhofer

Kühl

et al. 2020

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

These two authors contributed equally. AbstractObjective: To identify a pharmacological compound targeting macrophages, the most affected immune cells in inflammatory X-linked adrenoleukodystrophy (cerebral X-ALD) caused by ABCD1 mutations and involved in the success of hematopoietic stem cell transplantation and gene therapy. Methods: A comparative database analysis elucidated the epigenetic repressing mechanism of the related ABCD2 gene in macrophages and identified the histone deacetylase (HDAC) inhibitor Vorinostat as a compound to induce ABCD2 in these cells to compensate for ABCD1 deficiency. In these cells, we investigated ABCD2 and pro-inflammatory gene expression, restoration of defective peroxisomal boxidation activity, accumulation of very long-chain fatty acids (VLCFAs) and their differentiation status. We investigated ABCD2 and pro-inflammatory gene expression, restoration of defective peroxisomal ß-oxidation activity, accumulation of very long-chain fatty acids (VLCFA) and differentiation status. Three advanced cerebral X-ALD patients received Vorinostat and CSF and MRI diagnostics was carried out in one patient after 80 days of treatment. Results: Vorinostat improved the metabolic defects in X-ALD macrophages by stimulating ABCD2 expression, peroxisomal ß-oxidation, and ameliorating VLCFA accumulation. Vorinostat interfered with pro-inflammatory skewing of X-ALD macrophages by correcting IL12B expression and further reducing monocyte differentiation. Vorinostat normalized the albumin and immunoglobulin CSFserum ratios, but not gadolinium enhancement upon 80 days of treatment. Interpretation: The beneficial effects of HDAC inhibitors on macrophages in X-ALD and the improvement of the blood-CSF/blood-brain barrier are encouraging for future investigations. In contrast with Vorinostat, less toxic macrophage-specific HDAC inhibitors might improve also the clinical state of X-ALD patients with advanced inflammatory demyelination.

show abstract

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

Cited by 52 publications

References 34 publications

Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder

Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder

Clinical, Neuroimaging, Biochemical, and Genetic Features in Six Chinese Patients with Adrenomyeloneuropathy

Vorinostat in the acute neuroinflammatory form of X‐linked adrenoleukodystrophy

Contact Info

Product

Resources

About