Background: The phenotype associated with heterozygous HNF1A gene mutations has recently been extended to include neonatal hyperinsulinaemic hypoglycaemia (HH) in addition to maturity-onset diabetes of the young (HNF1AMODY).
Objective and hypotheses: The baby boy was born at 38th week of gestation; BW 4110 g; BL 53 cm (LGA). The mother had gestational diabetes; her father is treated for diabetes mellitus from the age of 50 years. The boy developed hypoglycaemia since the first day of life that required i.v. glucose administration; during hypoglycaemia (2.0 mmol/l) the level of insulin was not suppressed (4.2 mIU/l) confirming HH. After the neonatal period, hypoglycaemias resolved spontaneously. At age 10 months, the boy developed acute respiratory failure during viral pneumonia with severe dyspnoea; tachypnoea, and dehydration. At admission, he had hyperglycaemia 18 mmol/l prior to the first administration of corticosteroids and mild acidosis with dominant respiratory component. His HbA1c was 34 mmol/mol, and he had no history of polyuria and polydipsia. During the subsequent therapy with high-dose corticosteroids and mechanical ventilation, he required continuous insulin infusion for 7 days. Insulin therapy could be discontinued after the respiratory stabilization, afterwards the glycaemias remained normal. At the age of 12 months, HbA1c is in normal range (32 mmol/mol) without antidiabetic treatment.
Method: We performed molecular genetic testing of HNF4A and HNF1A genes using direct sequencing.
Results: In the proband a novel heterozygous mutation (L254Q) within the HNF1A gene was found. Mutation segregated with diabetes in three generations.
Conclusion: To our knowledge, this is the first observation of HNF1AMODY with history of neonatal hypoglycaemia followed by transient stress hyperglycaemia in infancy. This suggests that the capacity of β-cells to respond to high demands on insulin secretion may be impaired since an early age.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology