Genetic heterogeneity and challenges in the management of permanent neonatal diabetes mellitus: A single-centre study from South India

Abstract

Aim and Objectives: 1. To study the clinical outcome, growth and glycaemic control, 2. To study the frequency and type of genetic mutations. Methods: This is a retrospective study with a review of data of medical records from 2008 till date. Results: Twelve patients (six males) with neonatal diabetes mellitus (NDM) were identified. Median (interquartile range-(IQR)) age at diagnosis was 72 (31-95) days with a history of consanguinity in 75%. The median birth weight (range) was 2345 (900-3300) g. Follow-up data were available for eight patients with a median age at (IQR) follow-up of 3.3 (3-5.3) years. At follow-up, the mean annual HbA1c was 8.2% at a mean insulin dose of 1.1 U/kg/d. One patient with Wolcott-Rallison syndrome (WRS) and 21α-hydroxylase deficiency had poor growth and intellectual difficulty. The rest demonstrated satisfactory growth with an increase of mean weight centile from 2 nd to 13 th, height centile from 6.5 th to 20 th and normal neuro-cognitive development. Eleven patients underwent genetic testing with a molecular diagnosis in 54% (6/11): EIF2AK3 (n = 2) and one each in INS, PDX1, IL2RA and FOXP3. None had variants in ABCC8 or KCNJ11. One with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome underwent haematopoietic stem cell transplant (HSCT) and later succumbed. Conclusion: Our study demonstrates good clinical outcomes among NDM patients without immune dysfunction. Molecular diagnosis was attained only in around half of the patients (54%) with a great genetic heterogeneity.