The metabolomes of patients with paroxysmal nocturnal hemoglobinuria (PNH) are significantly different than that of healthy people, found a new study published in PLoS One

More precisely, the levels of the long-chain acylcarnitines metabolites were significantly higher in patients with PNH while glutamate, histidine, glutamine, taurine, aspartate, and phosphatidylcholines levels were significantly lower, the researchers noted.

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“Eculizumab infusion seemed to improve deficiencies in the acyl CoA metabolism and may have a role in the mitochondrial oxidative process of long and medium-chain fatty acids, reducing oxidative stress, and inflammation,” the study authors wrote.

“These differences suggest altered acylcarnitine balance, reduction in the amino acids participating in the glycogenesis pathway and impaired glutaminolysis,” the researchers wrote.

They quantified 186 specific annotated metabolites in 23 patients with PNH and 166 population-based controls. Their aim was to identify the biological pathways that are dysfunctional in PNH.

The researchers also analyzed the metabolic profiles of 12 patients with PNH before and after the administration of eculizumab to assess the effect of the treatment on biochemical pathways.

They found that the concentration of acylcarnitine C6:1, the ratio of C14:1 over C6, and the C4 over C6 ratio were significantly reduced before eculizumab treatment suggesting that the acyl CoA metabolism was impaired. However, 24 hours following eculizumab treatment levels were similar to healthy controls.

PNH is a rare hematologic disease characterized by chronic complement-mediated hemolysis. It is caused by a somatic mutation of the phosphatidylinositol glycan class A (PIGA) gene in hematopoietic stem cells resulting in a deficiency of glycosylphosphatidylinositol protein, which anchors other proteins to the surface of red blood cells.

Eculizumab, marketed under the brand name Soliris®, aims to treat PNH by blocking alternative complement pathways.


Yamakawa PE, Fonseca AR, Guerreiro da Silva IDC, et al. Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies. PLoS One. Published online August 1, 2023. doi:10.1371/journal.pone.0289285