Plasma phospholipid dysregulation in patients with cystathionine-β synthase deficiency

Alessandro Di Minno, Andrea Anesi, Mattia Chiesa, Ferdinando Cirillo, Gualtiero I. Colombo, Roberta C. Orsini, Filomena Capasso, Filomena Morisco, Susanna Fiorelli, Sonia Eligini, Viviana Cavalca, Elena Tremoli, Benedetta Porro, Matteo N.D. Di Minno

Research output: Contribution to journalArticlepeer-review


Background & aims: Patients with cystathionine β-synthase deficiency (CBSD) exhibit high circulating levels of homocysteine and enhanced lipid peroxidation. We have characterized the plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels. Methods and results: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, plasma lipids were determined with an untargeted lipidomics approach in 11 CBSD patients and 11 matched healthy subjects (CTRL). Compared to CTRL, CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p < 0.02), and depletion of phosphatidylcholine (PC; p = 0.02) and of lysophosphatidylcholine (LPC; p = 0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p = 0.015) and 5.3-fold (p = 0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r = 0.520; p = 0.019) was found. Conclusions: A novel biochemical abnormality in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE species is revealed by this lipidomic approach. Changes in plasma SAM and SAH concentrations are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, depletion of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with homocystinuria.

Original languageEnglish
Pages (from-to)2286-2295
Number of pages10
JournalNutrition, Metabolism and Cardiovascular Diseases
Issue number12
Publication statusPublished - Nov 27 2020


  • Homocystinuria
  • Phosphatidylethanolamine-N-methyltransferase
  • Plasma untargeted lipidomics
  • S-adenosylhomocysteine
  • S-adenosylmethionine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

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