Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience

Abstract

<b><i>Background:</i></b> Diabetes diagnosed within the first 6 months of life is defined as neonatal diabetes mellitus (NDM). Mutations in the <i>KCNJ11</i>, <i>ABCC8,</i> and <i>INS</i> genes are the most common cause of permanent NDM. In populations with a high rate of consanguinity, Wolcott-Rallison syndrome caused by biallelic <i>EIF2AK3</i> mutations is common. <b><i>Methods:</i></b> We studied the clinical characteristics and underlying genetic cause of disease in 15 individuals with diabetes onset before 6 months of age as defined by sustained hyperglycaemia requiring insulin treatment. Patients who had a remission of the diabetes, defined by a normal blood glucose and HbA1c value without insulin or sulphonylurea (SU) treatment, within the first 18 months of life were classified as having transient NDM (TNDM). <b><i>Results:</i></b> We report 15 patients with NDM from 14 unrelated families, including 10 with reported parental consanguinity. 1/15 patients had a remission of diabetes, leading to a diagnosis of TNDM. Mutations were detected in 80% (<i>n</i> = 12/15) of the cohort (<i>ABCC8</i> [<i>n</i> = 4], <i>PTF1A</i>-distal enhancer [<i>n</i> = 3], <i>KCNJ11</i> [<i>n</i> = 2], <i>EIF2AK3</i> [<i>n</i> = 1], <i>INS</i> [<i>n</i> = 1], and <i>SLC19A2</i> [<i>n</i> = 1]). All cases were initially treated with multiple dose insulin injections. One patient with an <i>ABCC8</i> mutation transitioned from insulin to SU resulting in improved metabolic control at the age of 20 years. <b><i>Conclusion:</i></b> Although the number of individuals born to consanguineous parents was considerably high in this cohort, KATP channel mutations (<i>ABCC8</i>/<i>KCNJ11</i>) were more common than <i>EIF2AK3</i> mutations (<i>n</i> = 6 vs. <i>n</i> = 1). Genetic analyses should be performed in all NDM cases due to the potential impact on treatment and prognosis.