# Application of high-resolution mass spectrometry profiling towards the diagnosis and acute management of maple syrup urine disease

## TL;DR

High-resolution mass spectrometry helps diagnose and manage maple syrup urine disease more effectively than traditional methods.

## Contribution

Demonstrates the utility of LC-HRMS metabolic profiling in diagnosing and monitoring maple syrup urine disease in infants.

## Key findings

- LC-HRMS detected elevated branched-chain amino acids and related metabolites in a 3-month-old with MSUD.
- LC-HRMS was used to monitor treatment progress in two infants with MSUD.
- Comprehensive metabolic profiling provides insights into metabolite changes during acute disease management.

## Abstract

The current approach for investigating patients with suspected inborn errors of metabolism (IEMs) involves traditional targeted biochemical assays such as amino/organic acid analyses. Although highly effective for confirmatory testing, they are less effective in identifying disorders not included in newborn screening (NBS) panels, and for patients with non-classical clinical presentations. Targeted assays analyze a narrow range of metabolites and are conducted across different analytical platforms, often requiring more than one specimen type. In contrast, comprehensive metabolic profiling using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) provides significantly more information from a single specimen, eliminating the need for multiple and time-consuming analyses across different platforms. We describe the use of LC-HRMS metabolic profiling in two patients with decompensated maple syrup urine disease (MSUD). In the first patient, a previously healthy 3-month-old infant presenting with altered mental status, apnea, and seizures, LC-HRMS analysis of plasma before treatment showed increased levels of branched-chain amino acids and their related 2-keto and hydroxy acids. The diagnosis of MSUD was confirmed by targeted amino acid analysis. Additionally, the treatment course, which included dialysis and nutritional management, was monitored using LC-HRMS. This approach was successfully applied to a second patient, a 1-week-old infant with classical MSUD identified through NBS. In conclusion, comprehensive metabolic profiling by LC-HRMS is a valuable investigative tool for patients with both classic and non-specific neurometabolic clinical phenotypes, providing additional insights into metabolite perturbations during acute management.