Hyperinsulinism–hyperammonemia syndrome in two Peruvian children with refractory epilepsy
-
Miguel Angel De los Santos-La Torre
,
Carlos Manuel Del Águila-Villar
,
Luis Rómulo Lu-de Lama
,
Oswaldo Nuñez-Almache
,
Eliana Manuela Chávez-Tejada
,
Oscar Antonio Espinoza-Robles
,
Paola Marianella Pinto-Ibárcena
,
Martha Rosario Calagua-Quispe
,
Pamela Miluska Azabache-Tafur
and
Rosa María Tucto-Manchego
Abstract
Objectives
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 GLUD1 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.
Case presentation
We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 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.
Conclusions
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.
Acknowledgments
We would like to thank Professor Sarah Flanagan and her genetic and biomolecular team at the Genomic Laboratory in University of Exeter, Medical School, UK, for their invaluable support with conducting the genetic analysis for our patients and facilitating us in the proper diagnosis and treatment of the patients.
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Research funding: The authors declare no financial support was received.
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Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Verbal and written informed consent was obtained from the parents of the patients.
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Ethical approval: The local Institutional Review Board approved this report.
References
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Articles in the same Issue
- Frontmatter
- Review
- One half-century of advances in the evaluation and management of disorders of bone and mineral metabolism in children and adolescents
- Original Articles
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- Sonic hedgehog N-terminal level correlates with adiponectin level and insulin resistance in adolescents
- Elevated amylase and lipase levels in patients with DKA followed in the pediatric intensive care unit
- The relationship between alexithymia, health literacy, and diet quality in obese adolescents
- The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome
- Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries
- Comparative characteristics of developing morphofunctional features of schoolchildren from different climatic and geographical regions
- Leucine tolerance in children with MSUD is not correlated with plasma leucine levels at diagnosis
- Outcomes of children with severe diabetic ketoacidosis managed outside of a pediatric intensive care unit
- Thiamine status during treatment of diabetic ketoacidosis in children – tertiary care centre experience
- Premature adrenarche in Prader–Willi syndrome is associated with accelerated pre-pubertal growth and advanced bone age
- Short Communication
- Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America
- Case Reports
- Pediatric growth hormone and prolactin-secreting tumor associated with an AIP mutation and a MEN1 variant of uncertain significance
- Two cases of MEGDHEL syndrome diagnosed with hyperammonemia
- Hyperinsulinism–hyperammonemia syndrome in two Peruvian children with refractory epilepsy
- A case report of a young boy with low renin and high aldosterone levels induced by Liddle syndrome who was previously misdiagnosed with primary aldosteronism
- Adolescents with type 1 diabetes vs. hybrid closed loop systems: a case series of patients’ behaviour that challenges the algorithm.
Articles in the same Issue
- Frontmatter
- Review
- One half-century of advances in the evaluation and management of disorders of bone and mineral metabolism in children and adolescents
- Original Articles
- Safety and user experience with off-label use of a flash glucose monitor (FreeStyle Libre® 1) among very young children with type 1 diabetes mellitus
- Sonic hedgehog N-terminal level correlates with adiponectin level and insulin resistance in adolescents
- Elevated amylase and lipase levels in patients with DKA followed in the pediatric intensive care unit
- The relationship between alexithymia, health literacy, and diet quality in obese adolescents
- The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome
- Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries
- Comparative characteristics of developing morphofunctional features of schoolchildren from different climatic and geographical regions
- Leucine tolerance in children with MSUD is not correlated with plasma leucine levels at diagnosis
- Outcomes of children with severe diabetic ketoacidosis managed outside of a pediatric intensive care unit
- Thiamine status during treatment of diabetic ketoacidosis in children – tertiary care centre experience
- Premature adrenarche in Prader–Willi syndrome is associated with accelerated pre-pubertal growth and advanced bone age
- Short Communication
- Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America
- Case Reports
- Pediatric growth hormone and prolactin-secreting tumor associated with an AIP mutation and a MEN1 variant of uncertain significance
- Two cases of MEGDHEL syndrome diagnosed with hyperammonemia
- Hyperinsulinism–hyperammonemia syndrome in two Peruvian children with refractory epilepsy
- A case report of a young boy with low renin and high aldosterone levels induced by Liddle syndrome who was previously misdiagnosed with primary aldosteronism
- Adolescents with type 1 diabetes vs. hybrid closed loop systems: a case series of patients’ behaviour that challenges the algorithm.
