A Review on the Cause, Clinical Presentation and Management of Most Common Types of Maturity Onset Diabetes of the Young (MODY)

Abstract

Maturity Onset Diabetes of the Young (MODY), first noticed by Andrew Cammidge in 1928, and first reported by Tattersall RB and Fajans SS (Father of MODY) in 1975, is a monogenic form of diabetes that is characterized by increased blood glucose level due to mutation of specific genes which are transferred from parent to child. Mutations in any of the transcription factors or the enzyme glucokinase or mainly hepatocyte nuclear factor genes lead to insufficient insulin release from pancreatic β- cells causing MODY. MODY was first used to characterize any asymptomatic hyperglycemia in children or young adults that did not progress to diabetic ketosis or ketoacidosis (a diabetic complication where the body produces excess ketone bodies). The diagnosis is usually made before the age of 25. MODY is frequently misdiagnosed as type 1 or type 2 diabetes mellitus, so for determining the treatment, a correct diagnosis for MODY is very important. Different types of MODY are identified based on the mutated genes. Molecular testing helps in confirming the type of MODY. The most frequent cause of MODY in all populations is due to the mutation in the GCK (Glucokinase), HNF1A (Hepatocyte nuclear factor 1 α), and HNF4A (Hepatocyte nuclear factor 4 α) which constitutes about 95% of all Maturity Onset Diabetes cases. This review summarizes the pathophysiology, diagnosis, and treatment options for the most common types of MODY i.e. GCK MODY, HNF1A MODY, HNF4A MODY.