Whole exome sequencing in energy deficiency inborn errors of metabolism: A systematic review

Abstract

Broad biochemical complexity and frequent overlapping clinical symptoms of inborn errors of metabolism (IEM), especially in energy-deficient patients, make accurate diagnosis difficult. In recent years, whole exome sequencing (WES), a comprehensive protein coding genetic test, has been used to diagnose patients at the molecular level. This study aims to evaluate the potential of WES in diagnosing energy-deficient IEM patients with limited biochemical findings and to identify common symptoms patterns in reported cases. Articles were identified using a combination of search terms in online databases (Science Direct, PubMed Central and Wiley). English-language case reports citing WES in the diagnosis of energy-deficient IEM patients were reviewed. This systematic review was conducted and reported using the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ checklist. The quality and risk of bias were assessed using Joanna Briggs Institute critical appraisal tool. A total of 37 studies comprising of 54 case reports were included in this review. The median age of the patients was 0.4 years, with 55.6% being male and 44.4% being female. A total of 33 mutant genes were reported and they related to either metabolism or mitochondrial function. WES was able to identify mutations in 53 of 54 cases reported. The diagnosis of energy-deficient IEM patients is crucial, particularly given the challenging range of diverse clinical symptoms they present. The high accuracy of the WES technique appears to improve the diagnostic process. Further research defining more detailed guidelines is needed to engage with this rare set of genetic diseases.

Keywords

• Rare genetic disorder
• Exome
• Biochemical genetic testing
• Energy deficiency
• Mitochondria