Angelman syndrome and isovaleric acidemia: What is the link?

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.

PMID: 26937393
PMCID: PMC4750580
DOI: 10.1016/j.ymgmr.2015.03.004

Angelman syndrome and isovaleric acidemia: What is the link?

Alix Lambrecht et al. Mol Genet Metab Rep. 2015.

. 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.

PMID: 26937393
PMCID: PMC4750580
DOI: 10.1016/j.ymgmr.2015.03.004

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.

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Figures

**Fig. 1**
Microsatellite analysis showing paternal isodisomy. The mother's electropherogram shows two peaks at 126 and 132 base pairs (bp) corresponding to her two alleles for marker D15S128. The father's profile shows 2 peaks, at 126 bp and 130 bp. The patient's profile presents only one peak at 130 bp corresponding to one of the paternal allele. None of the maternal alleles are present (126 or 132 bp) demonstrating the absence of maternal contribution. As MLPA ruled out a maternal deletion, the mechanism is paternal isodisomy.

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References

1. Kyllerman M. Angelman syndrome. Handb. Clin. Neurol. 2013;111:287–290. - PubMed
1. Van Buggenhout G., Fryns J.P. Angelman syndrome (AS, MIM 105830) Eur. J. Hum. Genet. 2009;17:1367–1373. - PMC - PubMed
1. Vockley J., Ensenauer R. Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity. Am. J. Med. Genet. C Semin. Med. Genet. 2006;142C:95–103. - PMC - PubMed
1. Ensenauer R., Vockley J., Willard J.M., Huey J.C., Sass J.O., Edland S.D., Burton B.K., Berry S.A., Santer R., Grunert S., Koch H.G., Marquardt I., Rinaldo P., Hahn S., Matern D. A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening. Am. J. Hum. Genet. 2004;75:1136–1142. - PMC - PubMed
1. Ferrer-Bolufer I., Dalmau J., Quiroga R., Oltra S., Orellana C., Monfort S., Rosello M., De La Osa A., Martinez F. Tyrosinemia type 1 and Angelman syndrome due to paternal uniparental isodisomy 15. J. Inherit. Metab. Dis. 2009;32(Suppl. 1):S349–S353. - PubMed

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Angelman syndrome and isovaleric acidemia: What is the link?

Affiliations

Angelman syndrome and isovaleric acidemia: What is the link?

Authors

Affiliations

Abstract

Figures

References