Early diagnosis of Congenital Hypothyroidism (CH) is critical to prevent irreversible neurodevelopmental damage. However, current TSH-based newborn screening using Dried Blood Spots (DBS) is limited by factors that lead to false-positive and false-negative results, necessitating the development of alternative methods. Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) as a high-throughput solution was investigated. This study presents a novel diagnostic approach utilizing DBS peptide barcoding, which was supported by comprehensive LC-MS/MS and network analysis. Peptide profiles showed a marked and reproducible difference between groups. MALDI-TOF MS identified a unique signature, including six dominant peptides specific to the CH-positive group. Subsequent analysis identified 37 candidate peptides, with network analysis linking 12 key proteins to established CH-related agents (e.g., thyroxine, TSHR). The MALDI-TOF MS peptidomic approach is validated as a robust, rapid, and cost-effective alternative for CH screening. This methodology represents a significant advance toward overcoming the limitations of current TSH assays and establishing a clinically translatable biomarker panel for improved personalized diagnosis of CH.
Phoungphosop et al. (Tue,) studied this question.