Exploratory metabolomic profiling of plasma and urine in patients with mucopolysaccharidosis type II (Hunter syndrome): A pilot study.

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked lysosomal storage disorder. It results from a deficiency of the enzyme iduronate-2-sulfatase (I2S), leading to the accumulation of glycosaminoglycans (GAGs) in various tissues and organs. Clinical manifestations include skeletal abnormalities, facial coarsening, organ enlargement, and developmental delays. The main objective of this study was to identify neuronopathic MPS II-specific biomarkers for early detection, diagnosis, monitoring, and follow up of affected patients. We thus applied liquid chromatography-high-resolution mass spectrometry (LC-HRMS) based untargeted metabolomic approaches to identify these potential biomarkers which could discriminate patients with the neuronopathic form of MPS II from healthy controls. Secondary aims focused on a better understanding of how the disease may affect the metabolome of patients. Urine and plasma samples from 21 untreated neuronopathic MPS II patients characterized by severe clinical manifestations were compared to 23 age- and gender-matched healthy control samples using a Xevo G2-XS Qtof MS (Waters Corp.). A comprehensive metabolomic workflow and multivariate statistical analyses revealed metabolites consistently elevated in MPS II patients. These include acylaminosugars, dipeptides, amino acids and their derivatives, lipid structures, and various compounds indicating disruptions in metabolic pathways. Development and validation of quantitative methods will be done using tandem mass spectrometry. Furthermore, identifying biomarkers associated with the central nervous system (CNS) in MPS II patients would help detect the neuronopathic form of the disease early, and enable the evaluation of the effectiveness of novel therapeutic strategies.