A case series of maturity onset diabetes of the young: Searching for a polar bear in a snowstorm

Abstract

Monogenic diabetes occurs due to a defect in a single gene or a chromosomal locus. The various modes of inheritance occurring include autosomal recessive, autosomal dominant, and non-Mendelian traits or can occur as a spontaneous case secondary to a de novo mutation. Although uncommon, monogenic diabetes accounts for 2.5–6% of diabetes in the paediatric age group and usually presents under 25 years of age. Monogenic diabetes can be classified into four major groups: (1) Maturity onset diabetes of the young (MODY), (2) neonatal and early infancy diabetes, (3) monogenic insulin resistance syndromes, and (4) diabetes affiliated with extra-pancreatic features. MODY is the most prevailing form of monogenic diabetes with an autosomal dominant inheritance. There are 14 subtypes of MODY that have been recognised now, and mutations in the genes hepatic nuclear factor 1-alpha (HNF1α) (MODY-3), glucokinase (MODY-2) HNF4α (MODY-1) account for about 95% of all MODY cases. According to a study in the UK, 80% of the MODY cases are misdiagnosed as either Type 1 or Type 2 diabetes mellitus. In our case series, we report 4 cases of MODY and compare their various characteristics. A genetic test was performed for children and adolescents with diabetes mellitus who had a strong history of diabetes in the family and tested negative for islet cell antibodies. Although there have been cases of MODY that have been previously reported worldwide, they usually fall under the types – MODY-3, MODY-2, and MODY-1, whereas we identified one adolescent with Kruppel-like factor-11 gene mutation giving rise to MODY-7 and two adolescents with paired box gene -4 gene mutation causing MODY-9, both of which contribute to <1% of the cases of MODY reported worldwide.