Genetic Heterogeneity and Challenges in the Management of Permanent Neonatal Diabetes Mellitus: A Single-Centre Study from South India

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.