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Licensed Unlicensed Requires Authentication Published by De Gruyter July 6, 2016

Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature

Dorotea Ninković ORCID logo, Vladimir Sarnavka, Anica Bašnec, Mario Ćuk, Danijela Petković Ramadža, Ksenija Fumić, Vesna Kušec, René Santer and Ivo Barić

Abstract

Hyperinsulinism-hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease characterized by recurrent hypoglycemia and persistent mild elevation of plasma ammonia. HI/HA syndrome is one of the more common forms of congenital hyperinsulinism (CHI), caused by activating mutations within the GLUD1 gene that encodes the mitochondrial enzyme glutamate dehydrogenase (GDH). We report here on monozygotic twin girls presented with fasting- and protein-induced hypoglycemia and mild persistent hyperammonemia. Genetic analysis revealed that both girls were heterozygous for a novel missense mutation within exon 11 [c.1499A>T, p.(R443W)] of the GLUD1 gene. Despite early treatment with diazoxide and a low protein diet, they both developed non-hypoglycemic seizures in early childhood followed by cognitive impairment. In addition to their clinical course, a review of the literature on HI/HA syndrome is provided.

Acknowledgments

We are grateful to Katja Dumić Kubat for her help with the literature.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work is part of the project “InNerMeD-I-Network” which was funded by the European Union, in the framework of the Health Programme. Sole responsibility lies with the author and the Executive Agency is not responsible for any use that may be made of the information contained therein.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-3-12
Accepted: 2016-5-9
Published Online: 2016-7-6
Published in Print: 2016-9-1

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