Mitochondrial Hepatopathies

Treem, William R.

doi:10.1016/b978-1-4377-0774-8.10071-5

Cited by 2 publications

(4 citation statements)

References 164 publications

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“…Up-regulation in the liver microsomal ω-oxidation pathway, which is characterized by elevations in the ratio of total dicarboxylic (AcylC-DC) to total esterified acylcarnitines (AcylC), is regarded as a rescue pathway in situations where β or α-oxidations are decreased [ 33 ]. Further support implicating shortages in mitochondrial function in PNH is that, in addition to β-oxidation impairments, ω-oxidation was also found to be significantly increased in PNH cases.…”

Section: Discussionmentioning

confidence: 99%

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Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies

Yamakawa,

Fonseca,

Guerreiro da Silva

et al. 2023

PLoS ONE

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Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disease of hematopoietic cells with a variable clinical spectrum characterized by intravascular hemolysis, high risk of thrombosis, and cytopenias. To understand the biochemical shifts underlying PNH, this study aimed to search for the dysfunctional pathways involved in PNH physiopathology by comparing the systemic metabolic profiles of affected patients to healthy controls and the metabolomic profiles before and after the administration of eculizumab in PNH patients undergoing treatment. Methods Plasma metabolic profiles, comprising 186 specific annotated metabolites, were quantified using targeted quantitative electrospray ionization tandem mass spectrometry in 23 PNH patients and 166 population-based controls. In addition, samples from 12 PNH patients on regular eculizumab maintenance therapy collected before and 24 hours after eculizumab infusion were also analyzed. Results In the PNH group, levels of the long-chain acylcarnitines metabolites were significantly higher as compared to the controls, while levels of histidine, taurine, glutamate, glutamine, aspartate and phosphatidylcholines were significantly lower in the PNH group. These differences suggest altered acylcarnitine balance, reduction in the amino acids participating in the glycogenesis pathway and impaired glutaminolysis. In 12 PNH patients who were receiving regular eculizumab therapy, the concentrations of acylcarnitine C6:1, the C14:1/C6 ratio (reflecting the impaired action of the medium-chain acyl-Co A dehydrogenase), and the C4/C6 ratio (reflecting the impaired action of short-chain acyl-Co A dehydrogenase) were significantly reduced immediately before eculizumab infusion, revealing impairments in the Acyl CoA metabolism, and reached levels similar to those in the healthy controls 24 hours after infusion. Conclusions We demonstrated significant differences in the metabolomes of the PNH patients compared to healthy controls. 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.

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Section: Discussionmentioning

confidence: 99%

“…is regarded as a rescue pathway in situations where β or α-oxidations are decreased [33]. Further support implicating shortages in mitochondrial function in PNH is that, in addition to βoxidation impairments, ω-oxidation was also found to be significantly increased in PNH cases.…”

Section: Plos Onementioning

confidence: 95%

Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies

Yamakawa,

Fonseca,

Guerreiro da Silva

et al. 2023

PLoS ONE

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“…Fulminant hepatic failure is a rare but devastating syndrome that results in the death of most children affected. If one includes not only fulminant hepatic failure secondary to infectious (probably viral) agents, drugs, and toxins but also includes those cases caused by inborn errors of metabolism and syndromes of unknown cause, at least several hundred children each year may be afflicted in the United States (1–4). Based on a recent, single, long‐term experience with fulminant hepatic failure, approximately 250 children are affected each year in the United States (5).…”

mentioning

confidence: 99%

“…In children, fulminant hepatic failure is the indication for 11% to 13% of liver transplantations compared with approximately 5% to 7% in adult patients (3). Prognostic data indicate that transplantation for fulminant hepatic failure is more critical for young children than for adults because patients younger than 10 years of age have less than a 10% survival rate without transplantation compared with 30% to 35% in patients between the ages of 10 and 40 years (2).…”

mentioning

confidence: 99%

Fulminant Hepatic Failure in Children

Treem

2002

J. pediatr. gastroenterol. nutr.

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Mitochondrial Hepatopathies

Cited by 2 publications

References 164 publications

Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies

Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies

Fulminant Hepatic Failure in Children

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