Metabolism / Liver / GI

Metabolic disorders, as well as congenital liver and intestinal disease, although rare, are an important cause of morbidity and mortality. The pathophysiology of these type of diseases is often not well understood, especially as the basic defect is not known yet. Our research group has been essential in identifying genes causing a number of these diseases: PFIC, ARC, MVID, STX3 deficiency, MCT1 deficiency, ARS deficiency, ANKZF1 deficiency, GLS hyperactivity and CHAPLE syndrome. Based on these discoveries new therapies could be developed and are still being developed.

Lifecycle and physical and mental development

Regular follow-up and evaluation of patients is being performed within the Sylvia Toth Center , a unique facility in which patients have a one day multidisciplinary and holistic work–up, not only including medical care (consultation by all required medical specialists) but also physical and mental evaluation (by a physical therapist and child psychologist).

Patient participation

Both patient care and research for patients with these diseases is being supported by the VKS (Vereniging voor Kinderen met Stofwisselingsziekten, Hanka Meutgeert), Stichting Metakids , the MLDS (Maag Lever Darm Stichting)Stofwisselkracht, as well as several private foundations aiming at improving the survival of patients with PFIC. Together they stimulate research for patients with congenital liver and intestinal diseases as well as guard patient interests through regular meetings.


The research teams of the department of pediatric gastroenterology (Prof. Dr. R.H.J. Houwen, Dr. W.L. van der Woerd) and the department of Metabolic Diseases (Dr. S.A. Fuchs and Dr. P.M. van Hasselt) are closely intertwined. They collaborate with the Laboratory of Metabolic diseases (Prof. Dr. N.M. Verhoeven-Duif) and the department of genetics (dr G van Haaften) to better understand the metabolic consequences of the diseases studied. Studying the pathophysiology and developing small molecule based therapies are mainly done using patient derived organoids at the laboratory of Pediatric Gastroenterology at the Hubrecht Institute  (Dr. S. Middendorp, Prof. Dr. E.E.A. Nieuwenhuis). For developing new cell based therapies (eg liver cell transplantation) a close collaboration with the Hubrecht Institute (Prof. Dr. H. Clevers) and the Faculty of Veterinary Medicine ( Dr. B. Spee) exists. In preparation for these clinical applications ethical aspects are being investigated in collaboration with Prof. Dr. A. Bredenoord. For both patient care and research there is recognition as an expertise center within the Netherlands, as well as internationally as a member of the relevant European Reference Networks.