Endocrine Abstracts

We present the case of a 36-year-old female with a focal neonatal hyperinsulinism diagnosed at birth in a context of hypoglycemia that was resistant to Diazoxide treatment. A subtotal pancreatectomy was performed and histology showed a focal hyperinsulinism. The mutation of ABCC8 was not searched at this point. The patient developed an insulin dependent diabetes at the age of 9 and required an insulin pump. In 2017 the patient was planning a pregnancy so she consulted a geneticist doctor for his opinion. Considering the patient’s history, a genetic test was performed that evidenced a local pancreatic recessive heterozygotic mutation for the ABCC8 gene (exon 39 c.4716C>A, p.Ser1572Arg). This phenotype is related to a uniparental disomy of a paternal origin situated at the pancreatic level. The geneticist concluded that the risk of transmission is very small (1/600) and was favorable for the pregnancy. As there was no consanguinity in the family, testing the father was not deemed necessary. A pregnancy starts in 2020 and at a gestational age of 28 weeks the mother goes into premature labor (premature rupture of membranes) and an emergency C-section is performed in April 2021 which concluded with the birth of bichorial bi amniotic male twins. Right after birth both babies experience severe hypoglycemia which requires a prolonged hospitalization with diazoxide treatment followed by an introduction of a somatostatin analogue treatment by pump and continuous enteral nutrition. The genetic tests evidenced the same two genetic mutations for both babies: exon 28 c63550del=p.Val1184 and exon 39 c.4716C>A=p.Ser1572Arg, which is responsible for a form of diffuse hyperinsulinism. As the already known mutation of ABCC8 was transmitted maternally, the greater risk lied in the transmission of a paternal heterozygotic mutation that was asymptomatic. This situation is very rare outside a consanguinity and was the consequence of the birth of two children that suffer from a severe diffuse hyperinsulinism which requires a somatostatin analogue pump treatment, as their insulin requiring diabetic mother is treated by an insulin pump.