Precision medicine for a man presented with diabetes at 2-month old

摘要

A 22-year-old man was referred for continuation of diabetes mellitus treatment. He was first diagnosed with diabetes mellitus 2 months after birth, when he failed to thrive and showed symptoms of diabetic ketoacidosis. There was no family history of diabetes mellitus. The patient did not exhibit the full set of features to be qualified for any developmental delay, epilepsy and neonatal diabetes mellitus (DEND) syndrome. Insulin replacement therapy was initiated; however, management was challenged by wide glycemic excursion, hypoglycemic unawareness and insulin-associated cutaneous lipo-hypertrophy. Reevaluation, including genetic testing, revealed a heterozygous missense p.Arg201Cys variation in the KCNJ11 gene encoding the potassium channel subunit Kir6.2. Successful treatment conversion from insulin to glibenclamide was achieved over an extended period of 2 months (up-titrating to a dose of 1.0 mg/kg) in this patient despite his long diabetes duration of 27 years with elimination of hypoglycemia unawareness and achievement of excellent glycemic control sustained over more than 5 years. This case highlights the importance of after having secured a firm genetic diagnosis, to undertake conversion to sulphonylurea with careful dose titration and perseverance over months. Confirmation of variants with functional implications by genetic testing in patients suspected of neonatal diabetes is important for accurate molecular diagnosis and precision-treatment strategy with optimal outcome.