Profiling of Serum Metabolites of Acute Intermittent Porphyria and Asymptomatic HMBS Mutation Carriers

Cells

Chia-Ni Lin¹  Chiung-Mei Chen²  Hung-Chou Kuo²  Ming-Shi Shiao³  Mei-Ling Cheng³ 

[1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;Linkou Medical Center, Department of Neurology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan;

关键词: porphobilinogen deaminase;    metabolomic profiling;    metabolic reprogramming;    heme metabolism;    δ-aminolevulinic acid;    porphobilinogen;   

DOI  :  10.3390/cells10102579

来源: DOAJ

【 摘 要 】

This study aims to present the serum metabolite profiles of patients with acute intermittent porphyria (AIP) and identify specific metabolites that could potentially discriminate between AIP, asymptomatic HMBS mutation carriers, and healthy individuals. The study cohort included 46 female participants: 21 AIP patients, 5 asymptomatic carriers, and 20 ‘normal’ participants (without HMBS gene mutation). Serum samples were analyzed for 157 selected metabolites or clinical variables using an assay combining liquid chromatography MS/MS and direct flow injection. AUC analysis was used to distinguish unique variables between the three groups. A total of 15 variables differed significantly between the AIP and normal control group (VIP score > 1.0 and p < 0.05 with FDR correction). In AIP patients, the levels tyrosine, valine, and eGFR were significantly lower, and the levels of sphingomyelin C16:0, C24:0, C24:1, phosphatidylcholine diacyl C32:1, C36:1, C36:3, ornithine, sarcosine, citrulline, blood urea nitrogen AST, and ALT were significantly higher. The AUC of these 15 variables in discriminating between normal and AIP patients ranged between 0.73 and 0.94 (p < 0.05). In conclusion, serum metabolic profiles differ between normal individuals and patients carrying the HMBS mutation. The unique metabolites associated with AIP identified in this study may be useful for monitoring the development of AIP symptoms.

【 授权许可】

Unknown