Congenital Hyperinsulinism and Evolution to Sulfonylurea-responsive Diabetes Later in Life due to a Novel Homozygous p.L171F ABCC8 Mutation

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Isik E., DEMİRBİLEK H., Houghton J. A., Ellard S., Flanagan S. E., Hussain K.

JOURNAL OF CLINICAL RESEARCH IN PEDIATRIC ENDOCRINOLOGY, vol.11, no.1, pp.82-87, 2019 (SCI-Expanded) identifier identifier identifier


Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. Recessive inactivating mutations in the ABCC8 and KCNJ11 genes account for approximately 50% of all CHI cases. Hyperinsulinaemic hypoglycaemia in infancy and diabetes in later life have been reported in patients with HNF1A, HNF4A and ABCC8 mutations. Herein, we present a child who was diagnosed with CHI at birth, then developed diabetes mellitus at the age of nine years due to a novel homozygous missense, p.L171 F (c.511C > T) mutation in exon 4 of ABCC8. The parents and one sibling were heterozygous carriers, whilst a younger sibling who had transient neonatal hypoglycemia was homozygous for the mutation. The mother and (maternal) uncle, who was also heterozygous for the mutation, developed diabetes within their third decade of life. The preliminary results of sulphonylurea (SU) treatment was suggestive of SU responsiveness. Patients with homozygous ABCC8 mutations can present with CHI in the newborn period, the hyperinsulinism can show variability in terms of clinical severity and age at presentation and can cause diabetes later in life. Patients with homozygous ABCC8 mutations who are managed medically should be followed long-term as they may be at increased risk of developing diabetes after many years.