Maturity Onset Diabetes of the Young

MODY is monogenic diabetes with autosomal dominant inheritance, onset usually before age 25, and absence of autoimmunity.

• Accounts for 1 to 2% of diabetes and is often misdiagnosed.
• Common types: GCK (MODY2, stable mild fasting hyperglycaemia 99 to 144 mg/dL), HNF1A (MODY3, sulfonylurea sensitive, renal glycosuria), HNF4A (MODY1), HNF1B (MODY5, renal cysts, genital anomalies).
• Neonatal diabetes and MODY share some genes (KCNJ11, ABCC8).
• Complications relate to hyperglycaemia; GCK carriers rarely develop them.

• Family history of diabetes across generations, onset before 25 to 35, non obese, no ketosis.
• GCK: asymptomatic, incidental; HNF1A: progressive hyperglycaemia in adolescence.
• HNF1B: renal cysts, uterine malformation, hypomagnesaemia, pancreatic atrophy.
• Low or normal C peptide without antibodies.

• Negative islet antibodies, detectable C peptide, family history.
• Genetic testing panel (GCK, HNF1A, HNF4A, HNF1B); MODY probability calculator.
• High sensitivity CRP is low in HNF1A MODY.
• Screen relatives with fasting glucose and genetic testing.

• GCK: no treatment; avoid medication except in pregnancy (insulin if fetus is unaffected and large).
• HNF1A and HNF4A: gliclazide 20 to 80 mg daily, low dose sulfonylureas first line; insulin when needed.
• HNF1B: insulin, manage renal disease and magnesium.
• Lifestyle advice, annual complication screening in non GCK types.
• Genetic counselling with 50% transmission risk.
• Pregnancy planning in HNF1A and HNF4A.