Proteomics in Inherited Metabolic Disorders

Abstract

Inherited metabolic disorders (IMD) are rare medical conditions caused by genetic defects that interfere with the body’s metabolism. The clinical phenotype is highly variable and can present at any age, although it more often manifests in childhood. The number of treatable IMDs has increased in recent years, making early diagnosis and a better understanding of the natural history of the disease more important than ever. In this review, we discuss the main challenges faced in applying proteomics to the study of IMDs, and the key advances achieved in this field using tandem mass spectrometry (MS/MS). This technology enables the analysis of large numbers of proteins in different body fluids (serum, plasma, urine, saliva, tears) with a single analysis of each sample, and can even be applied to dried samples. MS/MS has thus emerged as the tool of choice for proteome characterization and has provided new insights into many diseases and biological systems. In the last 10 years, sequential window acquisition of all theoretical fragmentation spectra mass spectrometry (SWATH-MS) has emerged as an accurate, high-resolution technique for the identification and quantification of proteins differentially expressed between healthy controls and IMD patients. Proteomics is a particularly promising approach to help obtain more information on rare genetic diseases, including identification of biomarkers to aid early diagnosis and better understanding of the underlying pathophysiology to guide the development of new therapies. Here, we summarize new and emerging proteomic technologies and discuss current uses and limitations of this approach to identify and quantify proteins. Moreover, we describe the use of proteomics to identify the mechanisms regulating complex IMD phenotypes; an area of research essential to better understand these rare disorders and many other human diseases.

Using metabolomics and proteomics to identify the potential urine biomarkers for prediction and diagnosis of gestational diabetes

“…MS-based absolute quantification has emerged as a successful alternative to immunoassays, offering lower cost, shorter turnaround time, and greatly improved throughput. 107 With the application of urine proteomics, a number of potential protein biomarkers for GDM have been identified in recent years.…”

Progress in Understanding Metabolic Syndrome and Knowledge of Its Complex Pathophysiology

“…This represents a potent instrument for investigating changes in disease-related pathways and discovering novel protein biomarkers. A proteomic biomarker is defined as "a specific peptide or protein associated with a particular ailment, such as the onset, manifestation, or progression of a disease or a response to treatment" or "a feature that is measured as an indicator of normal biological processes, pathogenic processes, or a response to an exposure or intervention" [81,82].…”

Progress on Understanding Metabolic Syndrome, and Knowledge of Its Complex Pathophysiology

“…This represents a potent instrument for investigating changes in disease-related pathways and discovering novel protein biomarkers. A proteomic biomarker is defined as "a specific peptide or protein associated with a particular ailment, such as the onset, manifestation, or progression of a disease or a response to treatment" or "a feature that is measured as an indicator of normal biological processes, pathogenic processes, or a response to an exposure or intervention" [80,81].…”