Background: Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with onset before 25 years. It is a heterogeneous disorder due to heterozygous monogenic mutations with an autosomal dominant transmission. It represents 2 to 5 percent of diabetes but is often underdiagnosed. We report three cases of MODY highlighting the features of different subtypes, two without associated abnormalities and one with renal disorder.
Cases presentation: Case 1: a nine-year-old boy with a BMI of 24.5 kg/m2 (> P97) presented with diabetes. IAA, ICA, GADA and IA2A were negative. Mutation c.392G>A (p.Arg131Gln) was found in the hepatocyte nuclear factor-1-alpha, which causes MODY 3. Initial treatment consisted of repaglinide but after two years, the patient requires insulin (0.8 U/kg/d). Case 2: a thirteen-year-old girl with a BMI of 22.8 kg/m2 (P 9097) presented with pre-diabetes. There were no insulin resistance. IAA, ICA, GADA and IA2A were negative. Mutation c.898G>A (p.Glu300Lys) was found in the glucokinase gene, which causes MODY 2. Metformin was given three times a day. Case 3: a nine-year-old Caucasian girl presented with diabetes. Medical history revealed bilateral renal dysplasia with renal insufficiency and renal graft. Homozygous mutation c.1235C>G (p.Pro412Arg) was found in the hepatocyte nuclear factor-1-beta gene, which causes MODY 5. Insulin was given twice daily (0.5 U/kg/d).
Conclusion: In MODY, mutations concern genes that are directly involved in the beta cell function. The symptoms manifest slowly with the absence of obesity and ketosis in most cases. MODY is usually treated by diet, oral diabetes medications and insulin. Treatment and prognosis vary depending on the genetic mutation. Clinicians should keep in mind the possibility of MODY, especially in antibody-negative youth with familial diabetes. Making a diagnosis of MODY can have important implications for the guidance of appropriate treatment, prognosis and genetic counselling.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology