Inborn Errors of Metabolism

Our research group studies rare genetic defects in metabolic pathways. We aim at a better understanding of pathomechanisms underlying such inborn errors of metabolism (IEM). Many metabolic diseases can result in early death or in severe handicaps, in particular, if patients are not treated in an adequate manner. Early diagnosis is a prerequisite for therapeutic approaches, which may enable normal development in some of those diseases. We continuously offer internships and thesis projects focused on analytical biochemistry (e.g., on the development of diagnostic tests) and on the characterization of IEM.

We have special interest in various IEM, for instance in those affecting the catabolism of branched-chain amino acids (including disorders of ketogenesis and ketolysis and HSD10 disease) and the metabolism of sulfur-containing amino acids. 

Following the detection of numerous N-acetylated amino acids in the patterns of urinary organic acids, we have been able to identify patients with a ‘novel’ inborn error of metabolism: Detailed investigations confirmed aminoacylase 1 deficiency on the enzyme level in lymphocytes and fibroblasts and in the ACY1gene. Subsequently, wild type and mutant enzymes were studied following overexpression in HEK293 cells. Our investigations comprise also studies on aspartoacylase (aminoacylase 2; ASPA). Disruption of this enzyme results in Canavan disease, a neurodegenerative disorder.

Phase 2 reactions increase the water solubility of compounds and thus facilitate their elimination. This can be achieved by conjugation of a coenzyme A (coA)-activated acid for instance with an amino acid molecule. Several enzymes (amino acid N-acyltransferases) may catalyze such reactions. Some of them have attracted our attention as they may have wide pharmacogenetic implications. Our research on IEM (supported, e.g., by the Heinz und Heide Dürr Stiftung, by the Gottfried und Julia Bangerter-Rhyner-Stiftung, and by the NRW state programs FH Basis and FH Struktur) is aiming at a better understanding of the roles of enzymes in health and disease.