Angelman syndrome and isovaleric acidemia: What is the link?

Alix Lambrecht; Samia Pichard; Hélène Maurey; Nuria Garcia Segarra; Séverine Drunat; Cécile Acquaviva-Bourdain; Sandrine Passemard; Jean-François Benoist; Anne-Laure Fauret-Amsellem; Manuel Schiff

doi:10.1016/j.ymgmr.2015.03.004

Angelman syndrome and isovaleric acidemia: What is the link?

Mol Genet Metab Rep. 2015 Mar 30:3:36-8. doi: 10.1016/j.ymgmr.2015.03.004. eCollection 2015 Jun.

Affiliations

¹ Katholieke Universiteit Leuven, Leuven, Belgium; Reference Center for Inborn Errors of Metabolism, Hôpital Robert Debré, APHP, Paris, France; Department of Child Neurology, Hôpital Robert Debré, APHP, Paris, France.
² Reference Center for Inborn Errors of Metabolism, Hôpital Robert Debré, APHP, Paris, France; Department of Child Neurology, Hôpital Robert Debré, APHP, Paris, France.
³ Department of Child Neurology, Hôpital Bicêtre, APHP, Le Kremlin Bicêtre, France.
⁴ Department of Genetics, Hôpital Robert Debré, APHP, Paris, France; Inserm U1141, Hôpital Robert Debré, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
⁵ Laboratory of Metabolic Biochemistry, HFME, HCL, Bron, France.
⁶ Department of Child Neurology, Hôpital Robert Debré, APHP, Paris, France; Department of Genetics, Hôpital Robert Debré, APHP, Paris, France; Inserm U1141, Hôpital Robert Debré, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
⁷ Reference Center for Inborn Errors of Metabolism, Hôpital Robert Debré, APHP, Paris, France; Laboratory of Metabolic Biochemistry, Hôpital Robert Debré, APHP, Paris, France.
⁸ Department of Genetics, Hôpital Robert Debré, APHP, Paris, France.
⁹ Reference Center for Inborn Errors of Metabolism, Hôpital Robert Debré, APHP, Paris, France; Department of Child Neurology, Hôpital Robert Debré, APHP, Paris, France; Inserm U1141, Hôpital Robert Debré, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.

Abstract

We report a toddler affected with Angelman syndrome and isovaleric acidemia (IVA). Such association was due to paternal uniparental isodisomy (UPD) of chromosome 15 in which the proband inherited two paternal copies of an IVA gene point mutation. As both diseases may have severe impact on neurodevelopment, adequate treatment of IVA should be discussed. In our patient however, the variant identified likely causes asymptomatic organic aciduria. Such findings emphasize that paternal UPD 15 can rarely lead to co-occurrence of Angelman syndrome and potentially treatable inborn errors of metabolism.

Keywords: Angelman syndrome; Isovaleric acidemia; Uniparental disomy of chromosome 15.