Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene.

Abstract

BACKGROUND:

Hyperinsulinism-hyperammonemia syndrome (HI/HA) is a rare autosomal dominant disorder presenting with hypoglycemia and hyperammonemia. It is caused by activating mutations in the GLUD1 gene.

CASE REPORTS:

Three patients from two different centers, a 14-month-old female, a 28-year-old female (mother of the first patient) from Toronto and an unrelated 2.5-year-old male from Vienna, presented with multiple episodes of seizures associated with hypoglycemia.

RESULTS:

All patients had mild to moderate hypoglycemia, inappropriate insulin levels and mild hyperammonemia, thus suggesting a disorder of glutamate dehydrogenase (GDH). Molecular genetic testing of the GLUD1 gene identified heterozygous mutations in all patients (patient 1 and her mother a novel c.1526G>C mutation; patient 3 a known c.809C>G mutation).

CONCLUSION:

We present three new patients with GDH caused by heterozygous mutation in the GLUD1 gene. Mild hyperammonemia and inappropriately elevated insulin levels should suggest a GLUD1 mutation. Early onset hypoglycemia associated with seizures, and especially a good response to diazoxide treatment, should include this disorder in the differential diagnosis of hyperinsulinemic hypoglycemia.

• Authors: Christel Tran, Vassiliky Konstantopoulou, Michelle Mecjia, Kusiel Perlman, Saadet Mercimek-Mahmutoglu, Jonathan B Kronick
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 28 Issue 7-8 Pg. 873-6 (Jul 2015) ISSN: 2191-0251 [Electronic] Germany
• PMID: 25781533 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamate Dehydrogenase
• GLUD1 protein, human

Topics

• Adult
• Child, Preschool
• Female
• Glutamate Dehydrogenase (genetics)
• Humans
• Hyperammonemia (complications, genetics, pathology)
• Hyperinsulinism (complications, genetics, pathology)
• Hypoglycemia (complications, genetics, pathology)
• Infant
• Male
• Mothers
• Mutation (genetics)
• Prognosis
• Seizures (diagnosis, etiology)
• Syndrome