Case Report

Pregnancy Complicated by Maternal MODY 3 and Paternal MODY 2 Diabetes and Subsequent Rapidly Falling Insulin Requirement

Table 2

MODY subtypes and pregnancy implications (4 most common subtypes in descending order of frequency).

Gene and MODY subtype in the motherGene Function + PhenotypePrognosisAssociated pregnancy implication

HNF1-alpha gene 
(MODY 3)
Regulates insulin gene transcription
Reduced insulin secretion/diabetes and marked sensitivity to sulfonylurea
Progressive  
May require insulin 
May develop secondary complications
Not associated with increased birthweight
Glucokinase (GCK) gene 
(MODY 2)
Catalyses conversion of glucose to glucose-6-phosphate
Reduced glucose sensing by beta cells – Mild diabetes
Generally non or slowly progressive 
Complications rare
Unaffected fetus—Excess fetal growth if no GCK mutation
Affected fetus—maternal hyperglycemia will be sensed as normal and result in normal growth
HNF4-alpha gene 
(MODY 1)
Nuclear transcription factor that regulates hepatic and pancreatic beta cell gene expression
Reduced insulin secretion/diabetes and marked sensitivity to sulfonylurea
Progressive  
May require insulin 
May develop secondary complications
Associated with increased birth weight (50% of babies), can cause neonatal hyperinsulinaemic hypoglycaemia
HNF1-beta gene 
(MODY 5)
Regulates HNF4á gene transcription
Insulin resistance + wide clinical spectrum 
+/- Urogenital/pancreatic anomalies 
+/- Pancreatic exocrine failure 
+/- Developmental delay/Learning difficulties
Progressive beta-cell failure with diabetes onset around puberty 
Insulin resistance without obesity 
Insulin dependence
In affected mother—possible pregnancy complications associated with genital and uterine malformations, such as recurrent miscarriages or preterm labour
For affected fetus—Urogenital malformations may be visible on prenatal ultrasound

Table 2 adapted from [7].