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Genetic basis of hyperlysinemia

Sander M Houten12*, Heleen te Brinke1, Simone Denis1, Jos PN Ruiter1, Alida C Knegt3, Johannis BC de Klerk4, Persephone Augoustides-Savvopoulou5, Johannes Häberle6, Matthias R Baumgartner6, Turgay Coşkun8, Johannes Zschocke9, Jörn Oliver Sass107, Bwee Tien Poll-The2, Ronald JA Wanders12 and Marinus Duran12

Author Affiliations

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

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Orphanet Journal of Rare Diseases 2013, 8:57  doi:10.1186/1750-1172-8-57

Published: 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.

Inborn errors of metabolism; Hyperlysinemia; Lysine; Contiguous gene deletion syndrome