Serum Metabonomics Reveals Key Metabolites in Different Types of Childhood Short Stature

Abstract

Nowadays, short stature (SS) in childhood is a common condition encountered by pediatricians, with an increase in not just a few families. Various studies related to the variations in key metabolites and their biological mechanisms that lead to SS have increased our understanding of the pathophysiology of the disease. However, little is known about the role of metabolite variation in different types of childhood SS that influence these biological processes and whether the understanding of the key metabolites from different types of childhood SS would predict the disease progression better. We performed a systematic investigation using the metabonomics method and studied the correlation between the three groups, namely, the control, idiopathic short stature (ISS), and short stature due to growth hormone deficiency (GHD). We observed that three pathways (viz., purine metabolism, sphingolipid signaling pathway, and sphingolipid metabolism) were significantly enriched in childhood SS. Moreover, we reported that two short peptides (Thr Val Leu Thr Ser and Trp Ile Lys) might play a significant role in childhood SS. Various metabolites in different pathways including 9,10-DiHOME, 12-HETE, 12(13)-EpOME, arachidonic acid methyl ester, glycerophospho-N-arachidonoyl ethanolamine, curvulinic acid (2-acetyl-3,5-dihydroxyphenyl acetic acid), nonanoic acid, and N'-(2,4-dimethylphenyl)-N-methylformamidine in human serum were compared between 60 children diagnosed with SS and 30 normal-height children. More investigations in this area may provide insights and enhance the personalized treatment approaches in clinical practice for SS by elucidating pathophysiology mechanisms of experimental verification.

Metabolic Characteristics and Discriminative Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature in Preadolescents and Adolescents

“…Our previous study based on nuclear magnetic resonance (NMR) metabolomics found that disturbed glucose metabolism and metabolism and biosynthesis of amino acids were typical metabolic features of SS caused by GHD [10]. A study on 31 children with GHD and 29 children with ISS by ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF-MS)-based serum metabolomics found that purine metabolism, the sphingolipid signaling pathway, and sphingolipid metabolism were significantly enriched in childhood SS [11]. However, most of these studies focused on SS in preadolescents, and the metabolic information of adolescent SS was lacking.…”