Poster Presentation ESA-SRB 2023 in conjunction with ENSA

A tale of two sisters – delayed diagnosis of hypoglycaemia (#342)

Felicity Stringer 1 , Christopher Preston 1 2 , Richard MacIsaac 1 , Fiona Inchley 1 , Livia Rivera-Woll 3 , Stephen Farrell 1 , Eric Yong 1 , NIrupa Sachithanandan 1
  1. St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
  2. Western Health, Melbourne, Victoria, Australia
  3. Endocrinology Melbourne, Melbourne, Victoria, Australia

Case
A 47-year-old female presents with worsening neuroglycopenic symptoms of hypoglycaemia. The symptoms occur fasting and post-prandial, and improve with correction of hypoglycaemia.
Her past medical history was significant for neonatal hypoglycaemia, and she had an elder sister with an intellectual disability secondary to severe neonatal hypoglycaemia.
Initial screening pathology was unremarkable, however an inpatient 72-hour fast revealed hyperinsulinaemic hypoglycaemia, and she was commenced on diazoxide.
Due to her family history, genetic testing was undertaken, which was positive for ABCC8 compound heterozygote mutation.
Unfortunately she did not tolerate diazoxide or acarbose medication. She continues to manage with dietary modifications aimed at avoiding hypoglycaemia, assisted by the use of a continuous glucose monitor.
Her sister has subsequently been further investigated and her 72-hour fast showed hyperinsulinaemic hypoglycaemia. Genetic testing revealed the same ABCC8 compound heterozygote mutation, and testing of their father (with their mother being deceased) is currently being undertaken.

Discussion
Monogenic hyperinsulinaemia effects 1/50,000 live births, and the most severe forms are caused by an inactivating mutation of the ABCC8 and KCNJ11 genes [1,2]. Together these genes are responsible for 36–70% of congenital hyperinsulinism cases [3-5].
ABCC8 and KCNJ11 encode the two subunits of the potassium-ATP channel [2]. This channel is critical in controlling glucose mediated release of insulin from pancreatic beta-cells, and dysfunction leads to dysregulated insulin secretion [2,4]. Patients typically present in early infancy with seizures, coma, and failure to thrive, with severe fasting hypoglycaemia [1].
Treatment for these patients includes somatostatin receptor analogues, and dietary modification [4,6]. Continuous glucose monitoring can be extremely beneficial at giving patients autonomy to manage their disease, and relieving anxiety associated with hypoglycaemia. Due to the mechanism of action of the medication, homozygous or compound heterozygous recessive mutations in the ABCC8 gene are unresponsive to diazoxide [1,2].

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