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. 2020 Nov;11(4):207-216.
doi: 10.1159/000510171. Epub 2020 Sep 16.

Hyperinsulinemic Hypoglycemia in a Patient with Costello Syndrome: An Etiology to Consider in Hypoglycemia

Dogus Vuralli  1 , Can Kosukcu  2 , Ekim Taskiran  2 , Pelin Ozlem Simsek-Kiper  3 , Gulen Eda Utine  3 , Koray Boduroglu  3 , Ayfer Alikasifoglu  1 , Mehmet Alikasifoglu  2   3
Affiliations

Hyperinsulinemic Hypoglycemia in a Patient with Costello Syndrome: An Etiology to Consider in Hypoglycemia

Dogus Vuralli et al. Mol Syndromol. 2020 Nov.

Abstract

Several endocrine disorders have been defined in patients with Costello syndrome (CS). In this report, we describe a patient with CS accompanied by a clinical picture of hyperinsulinemic hypoglycemia responsive to diazoxide treatment. A 41-day-old female patient with a birth weight of 3,600 g was referred for atypical facial features and swallowing dysfunction. She had a weight of 4,000 g (-0.8 SDS), a length of 50 cm (-2.4 SDS), and a head circumference of 38 cm (0.2 SDS). The clinical findings were suggestive of a genetic syndrome, mainly a RASopathy or Beckwith-Wiedemann syndrome. Whole exome sequencing revealed a de novo heterozygous missense variant in the HRAS (NM_001130442) gene in exon 2: c.35G>C; p.(Gly12Ala), establishing the molecular diagnosis of CS. The patient developed symptomatic hypoglycemia (jitteriness and sweating) at the age of 13 months. The patient's serum glucose was 38 mg/dL with simultaneous serum insulin and C-peptide levels, 2.8 μIU/mL and 1.8 ng/mL, respectively. Hyperinsulinism was suspected, and an exaggerated glucose response was detected in a glucagon test. Blood glucose monitoring indicated episodes of fasting hypoglycemia and postprandial hyperglycemia. Diazoxide of 10 mg/kg/day was initiated in 3 doses for hyperinsulinemic hypoglycemia, which resolved without new episodes of postprandial hyperglycemia. The patient deceased at the age of 17 months due to cardiorespiratory failure in the course of severe pneumonia complicated with pulmonary hypertension and hypertrophic cardiomyopathy. Several genetic syndromes including CS are associated with endocrinologic manifestations including abnormal glucose homeostasis. Although the frequency and underlying mechanisms leading to hyperinsulinemic hypoglycemia are yet unknown, hypoglycemia in CS responds well to diazoxide.

Keywords: Costello syndrome; Diazoxide; Hyperinsulinism; Hypoglycemia; RASopathy.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Clinical photo of the patient.
See this image and copyright information in PMC

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