Early-onset, severe lipoatrophy in a patient with permanent neonatal diabetes mellitus secondary to a recessive mutation in the INS gene

Abstract

We describe a case of neonatal diabetes due to a homozygous mutation (c.3 G>T) at the INS gene, leading to lack of insulin expression and severe hyperglycemia from day one of life requiring permanent insulin replacement therapy. The genetic loss of endogenous insulin production likely led to lack of immune tolerance to insulin, with resultant autoantibody production against exogenous insulin and progressive immune-mediated lipoatrophy at injection sites.

The value of in vitro studies in a case of neonatal diabetes with a novel Kir6.2‐W68G mutation

“…Nearly half (46%) of patients with neonatal diabetes mellitus (NDM) have a gain-of-function mutation in either the Kir6.2 ( KCNJ11 ) or SUR1 ( ABCC8 ) subunit of the ATP-sensitive potassium (K ATP ) channel 1 , 2 . Approximately, 31% of cases are due to mutations in KCNJ11 and approximately 13% are due to mutations in ABCC8 3 , 4 . The majority of patients with NDM caused by previously described K ATP mutations respond to sulphonylurea therapy, allowing transition off subcutaneous insulin 5 , 6 .…”