Open Access Research

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

Abstract

Background

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.

Methods

We collected the clinical, biochemical and molecular data in a cohort of 8 hyperlysinemia patients with distinct neurological features.

Results

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.

Conclusions

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.

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