Hyperinsulinism-hyperammonemia syndrome in two Peruvian children with refractory epilepsy

• Published in: Journal of pediatric endocrinology & metabolism : JPEM Vol. 36; no. 2; p. 207
• Main Authors: De Los Santos-La Torre, Miguel Angel, Del Águila-Villar, Carlos Manuel, Lu-de Lama, Luis Rómulo, Nuñez-Almache, Oswaldo, Chávez-Tejada, Eliana Manuela, Espinoza-Robles, Oscar Antonio, Pinto-Ibárcena, Paola Marianella, Calagua-Quispe, Martha Rosario, Azabache-Tafur, Pamela Miluska, Tucto-Manchego, Rosa María
• Format: Journal Article
• Language: English
• Published: Germany 23-02-2023
• Subjects: Child; Congenital Hyperinsulinism - complications; Congenital Hyperinsulinism - diagnosis; Congenital Hyperinsulinism - drug therapy; Diazoxide - therapeutic use; Drug Resistant Epilepsy; Epilepsy - drug therapy; Epilepsy - genetics; Glutamate Dehydrogenase - genetics; Humans; Hyperinsulinism - complications; Hyperinsulinism - diagnosis; Hyperinsulinism - genetics; Mutation; Peru; Peru; epilepsy; hyperammonemia; congenital hyperinsulinism; hypoglycemia
• ISSN: 2191-0251
• DOI: 10.1515/jpem-2022-0490

Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized.  Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the
gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management.
We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the
gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru.
HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.