Does renal GCDH expression contribute to the explanation of the two excretor types in glutaric aciduria type I?

Abstract

This Master Thesis was carried out at the University of Lausanne and is part of the master's curriculum in the School of Medicine(1). All manipulations have been done at the laboratory of the "Centre des Maladies Moléculaires" (CMM) which is part of the "Département Médico-Chirurgical de Pédiatrie" (DMCP) at the "Centre Hospitalier Universitaire Vaudois" (CHUV) (2). One of the research groups of the CMM works on fundamental and translational research on organic acidurias, mainly on glutaric aciduria type 1 (GA-1) and methylmalonic aciduria with a special focus on the understanding of pathophysiological mechanisms leading to brain damage in these diseases (2-5). The research exposed below is part of a subproject of the research on GA-1 which aims to understand the physiological role of GCDH in proximal tubular cells of the kidney and to elucidate whether its presence in these specific cells might be the explanation for the existence of two excretor types (low and high excretors) in GA-I patients (6)