Prof. Dr. med. Johannes Häberle

 

Main Goals, Keywords

• Urea cycle disorders: to understand phenotypic variability
  
• Glutamine synthetase deficiency: to understand the pathophysiology
  and find a way to treat

Group Members

1 group leader, 1 PhD student, 2 technicians

Previous, Current and Future Research

Urea cycle disorders: Molecular basis and pathology of phenotypic variability. In other words: why are patients affected by urea cycle disorders so different? Some die from cerebral edema during the first hyperammonemic episode as newborns and some present with mild neurological disease late in adulthood.

Glutamine Synthetase deficiency: this is an extremely rare inborn error of metabolism affecting mainly brain development caused by systemic glutamine deficiency. We don’t yet fully understand the pathophysiology and there is currently no treatment.

Future Projects

For urea cycle disorders, we test the influence of aspartate and of carbamylglutamate on the function of recombinant proteins derived from eukaryotic expression.

For glutamine synthetase, we investigate the role of glutamine deprivation for many metabolites and test the use of glutamine substitution in vivo.

Techniques and Equipment

Molecular biology including eukaryotic expression of recombinant wildtype and mutant proteins, biochemistry, cell culture under varying conditions; individualized clinical trials in selected patients.

Selected Publications

• Klaus V, Vermeulen T, Minassian B, Israelian N, Engel K, Lund AM, Roebrock K, Christensen E, Häberle J (2009) Highly variable clinical phenotype of carbamylphosphate synthetase 1 deficiency in one family: an effect of allelic variation in gene expression? Clin Genet 75: 263-269
  
  
• Häberle J, Shahbeck N, Ibrahim K, Hoffmann GF, Ben-Omran T (2011) Natural course of glutamine synthetase deficiency in a 3 year old patient, Mol Genet Metab, in press
  
  
• Häberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, Eeds A, Willis A, Yadav M, Summar S, and the Urea Cycle Disorders Consortium, Lichtarge O, Rubio V, Wong LJ, Summar M (2011) Molecular Defects in Human Carbamoyl Phosphate Synthetase I: Mutational Spectrum, Diagnostic and Protein Structure Considerations, Hum Mutat, in press
  

Funding

Swiss National Science Foundation

URL

http://www.kispi.unizh.ch/Kinderspital/Medizin/Medizin/Stoffwechsel_de.html