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

Background: Diabetes diagnosed within the first 6 months of life is defined as neonatal diabetes mellitus (NDM). Mutations in the KCNJ11, ABCC8, and INS genes are the most common cause of permanent NDM. In populations with a high rate of consanguinity, Wolcott-Rallison syndrome caused by biallelic EIF2AK3 mutations is common.

Methods: 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).

Results: 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% (n = 12/15) of the cohort (ABCC8 [n = 4], PTF1A-distal enhancer [n = 3], KCNJ11 [n = 2], EIF2AK3 [n = 1], INS [n = 1], and SLC19A2 [n = 1]). All cases were initially treated with multiple dose insulin injections. One patient with an ABCC8 mutation transitioned from insulin to SU resulting in improved metabolic control at the age of 20 years.

Conclusion: Although the number of individuals born to consanguineous parents was considerably high in this cohort, KATP channel mutations (ABCC8/KCNJ11) were more common than EIF2AK3 mutations (n = 6 vs. n = 1). Genetic analyses should be performed in all NDM cases due to the potential impact on treatment and prognosis.