Precision diagnostics and exploration of disease mechanisms in Inborn Errors of Metabolism

Diagnostics of rare diseases is currently being transformed due to technological breakthroughs in high-throughput methodologies such as massive parallel DNA sequencing.

We have built a strong translational environment, combining multidisciplinary clinical competence with highly specialized biochemistry, high-throughput genomics and basic experimental science.

Through this integrated approach, we have implemented whole genome sequencing (WGS) into acute clinical medicine, with a strong focus on inborn errors of metabolism, a group of around one thousand different monogenic diseases with a wide spectrum of presentation.

Results are dramatic as new patient groups receive specific diagnoses enabling early, specific treatments sometimes preventing early death or severe brain damage.

Future plans are to improve performance of clinical WGS, to add RNA sequencing and proteomics to further improve diagnostic yield, and to develop biomarkers for stratification of patients and monitoring of treatment response.

We are also developing combined, integrated analyses of genomic, transcriptomic, proteomic, biochemical and clinical data, to further increase diagnostic yield and identify biological pathways relevant for disease. Genotype-phenotype relationships are explored and long-term follow-up of patients is performed.

Novel disease genes are discovered and detailed pathogenetic mechanisms are investigated in patient cells and tissues, and in models using reprogrammed cells, flies and mice.