Genetic basis of hyperlysinemia
1 Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, AZ 1105, The Netherlands
2 Department of Pediatrics, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
3 Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
4 Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands
5 University 1st Department of Pediatrics, Metabolic Laboratory, Hippocration General Hospital of Thessaloniki, Thessaloniki, Greece
6 Division of Metabolism, University Children’s Hospital Zürich, Zürich, Switzerland
7 Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zürich, Zürich, Switzerland
8 Unit of Metabolism, Hacettepe University Faculty of Medicine, Ankara, Turkey
9 Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria
10 University Children’s Hospital Freiburg, Freiburg, Germany
Orphanet Journal of Rare Diseases 2013, 8:57 doi:10.1186/1750-1172-8-57Published: 9 April 2013
Hyperlysinemia is an autosomal recessive inborn error of L-lysine degradation. To date only one causal mutation in the AASS gene encoding α-aminoadipic semialdehyde synthase has been reported. We aimed to better define the genetic basis of hyperlysinemia.
We collected the clinical, biochemical and molecular data in a cohort of 8 hyperlysinemia patients with distinct neurological features.
We found novel causal mutations in AASS in all affected individuals, including 4 missense mutations, 2 deletions and 1 duplication. In two patients originating from one family, the hyperlysinemia was caused by a contiguous gene deletion syndrome affecting AASS and PTPRZ1.
Hyperlysinemia is caused by mutations in AASS. As hyperlysinemia is generally considered a benign metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PTPRZ1. Our findings illustrate the importance of detailed biochemical and genetic studies in any hyperlysinemia patient.