Aim: Hypoglycemia in childhood is very rare and can be caused by genetic mutations or insulin-secreting neoplasms. Postprandial hypoglycemia has previously been associated with insulin receptor (INSR) gene mutations. We aimed to identify the cause of postprandial hypoglycemia in a 10-year-old boy. Subjects: We studied the symptomatic proband and his apparently asymptomatic mother and elder brother. All of them were lean. Methods: Metabolic screening of the proband included a 5-hour oral glucose tolerance test (OGTT), angio-magnetic resonance imaging, and 18F-dihydroxyphenylalanine positron emission tomography/computed tomography imaging of the pancreas. INSR gene sequencing and in vitro functional studies of a novel INSR mutation were also undertaken. Results: Fasting hyperinsulinemia was detected during metabolic screening, and 5-hour OGTT showed hypoglycemia at 2400 in the proband, his mother, and brother. Pancreatic imaging showed no evidence of neoplasia. Acanthosis nigricans with high fasting insulin levels in the proband suggested severe insulin resistance and prompted INSR gene sequencing, which revealed the novel, heterozygous p.Phe1213Leu mutation in the patient and his family members. In vitro studies showed that this mutation severely impairs insulin receptor function by abolishing tyrosine kinase activity and downstream insulin signaling. Conclusions: The identification of etiological cause of hypoglycemia in childhood may be challenging. The combination of fasting hyperinsulinemia with acanthosis nigricans in a lean subject with hypoglycemia suggests severe insulin resistance and warrants INSR gene screening.

Innaurato, S., Brierley, G., Grasso, V., Massimi, A., Gaudino, R., Sileno, S., et al. (2018). Severe insulin resistance in disguise: a familiar case of reactive hypoglycemia associated with a novel heterozygous INSR mutation. PEDIATRIC DIABETES, 19(4), 670-674 [10.1111/pedi.12632].

Severe insulin resistance in disguise: a familiar case of reactive hypoglycemia associated with a novel heterozygous INSR mutation

Grasso Valeria;SILENO, SARA;Bernardini Sergio;Barbetti Fabrizio.
2018-02-07

Abstract

Aim: Hypoglycemia in childhood is very rare and can be caused by genetic mutations or insulin-secreting neoplasms. Postprandial hypoglycemia has previously been associated with insulin receptor (INSR) gene mutations. We aimed to identify the cause of postprandial hypoglycemia in a 10-year-old boy. Subjects: We studied the symptomatic proband and his apparently asymptomatic mother and elder brother. All of them were lean. Methods: Metabolic screening of the proband included a 5-hour oral glucose tolerance test (OGTT), angio-magnetic resonance imaging, and 18F-dihydroxyphenylalanine positron emission tomography/computed tomography imaging of the pancreas. INSR gene sequencing and in vitro functional studies of a novel INSR mutation were also undertaken. Results: Fasting hyperinsulinemia was detected during metabolic screening, and 5-hour OGTT showed hypoglycemia at 2400 in the proband, his mother, and brother. Pancreatic imaging showed no evidence of neoplasia. Acanthosis nigricans with high fasting insulin levels in the proband suggested severe insulin resistance and prompted INSR gene sequencing, which revealed the novel, heterozygous p.Phe1213Leu mutation in the patient and his family members. In vitro studies showed that this mutation severely impairs insulin receptor function by abolishing tyrosine kinase activity and downstream insulin signaling. Conclusions: The identification of etiological cause of hypoglycemia in childhood may be challenging. The combination of fasting hyperinsulinemia with acanthosis nigricans in a lean subject with hypoglycemia suggests severe insulin resistance and warrants INSR gene screening.
7-feb-2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/13 - ENDOCRINOLOGIA
English
Con Impact Factor ISI
Innaurato, S., Brierley, G., Grasso, V., Massimi, A., Gaudino, R., Sileno, S., et al. (2018). Severe insulin resistance in disguise: a familiar case of reactive hypoglycemia associated with a novel heterozygous INSR mutation. PEDIATRIC DIABETES, 19(4), 670-674 [10.1111/pedi.12632].
Innaurato, S; Brierley, G; Grasso, V; Massimi, A; Gaudino, R; Sileno, S; Bernardini, S; Semple, R; Barbetti, F
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
SIR in disguise.pdf

solo utenti autorizzati

Tipologia: Versione Editoriale (PDF)
Licenza: Copyright dell'editore
Dimensione 886.39 kB
Formato Adobe PDF
886.39 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/208518
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 7
social impact