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Hyperinsulinemic Hypoglycemia Due to Homozygous C.706 C>T (P. R236X) Mutation in 3 Siblings: Presentation with Resistant Epilepsy

  • Atilla Çayır
  • Elisa De Franco
  • Ufuk Utku Güllü
  • Sarah E. Flanagan
  • Sian Ellard
  • Hüseyin Demirbilek

J Clin Res Pediatr Endocrinol 2017;9(1):29-29

Hyperinsulinemic hypoglycemia (HH) is the most common cause of severe resistant hypoglycemia in newborn, infancy, and childhood period. Diazoxide is the mainstay of medical therapy in HH. In about half of patients, HH is diazoxide-unresponsive. Mutations in HADH gene cause diazoxide-responsive and protein-sensitive HH. Although HADH mutations can present with severe neonatal hypoglycemia, they usually present at infancy and childhood period with relatively mild hypoglycemia. A 17-year-old male patient with the diagnosis of core triatriatum was admitted to our pediatric cardiology department for cardiac catheterization. He had epilepsy and neuro-developmental delay and was on triple-antiepileptic therapy. During his hospitalization period, one of his sisters developed generalized tonic-clonic seizure. Blood glucose level measured was 32 mg/dL with a simultaneous insulin level of 28.8 mIU/mL and C-peptide of 2.8 ng/mL. Urine ketone test was negative. Further evaluation of our patient revealed hypoglycemia with serum insulin level of 22.2 mIU/mL and C-peptide of 2.4 ng/mL. A diagnosis of HH was considered. Parents were second cousins. Another female patient also suffered from epileptic seizures-like episodes. Two sisters had died at 3-month-old and 1-year-old. Molecular genetics analysis revealed homozygous nonsense, c.706C>T(p.R236X) mutation in exon-6 of HADH gene. Parents were heterozygous. Diazoxide therapy was commenced for the siblings with homozygous mutation. The frequency of epileptic seizures in patient on antiepileptic therapy was decreased, while other siblings remained free of seizure during follow-up. We had planned to perform a protein loading test. In conclusion, since HH due to HADH gene mutations can present during childhood period, it should be kept in mind in the differential diagnosis of resistant epilepsy, particularly in consanguineous pedigrees.