Neonatal diabetes (ND), classified as either permanent (PND) or transient (TND), occurs in 1/200,000 live births. In 50% cases of TND, remission presents within the first year of life, only to relapse later before puberty in 50% of cases. The most frequent cause is mutation of the 6q24 gene accompanied by mutations in heterozygosis of ABCC8 gene. 80% of mutations in this gene are in novo, due to autosomal recessive inheritance. Such cases respond to treatment with sulfonylurea (SU). We present a case of TND that motivated the change of diagnosis in both (mother and baby).
Material and method: A term male infant was born at 38 weeks gestation, weighing 2660gr (10-25th centile), length: 48 cm (40th centile). Presented isolated hyperglycemia in the first 48 hours, with true hyperglycemia on the 4th day, requiring treatment with Actrapid 0.2 UI/KG/D. One month later the insulin requirements were 0.20.3 UI/kg/d. FH: Non-Consanguinean parents. Type 1 DM mother at 9 years old, onset with hyperglycemia, requiring insulin treatment. Maternal grandmother at 38 years old, was diagnosed with Type I Diabetes requiring insulin treatment. Laboratory tests: Glucose: 300 mg/dl, HBA1c 4.7%, no ketonuria, C-Peptide; 0.58 ng/dl, Fasting insulin: 0.6mUI/ml. Negative diabetes antibodies (Anti-GAD, Islet, insulin autoantibodies) in mother and neonate. Genetic study of both: mutation in heterozygosis of exon 21 of the ABBC8 gene (p.C24982G>C,Gly.833G>Ala), associated with PND. A glycaemic control and study of pancreatic reserve (prior to the transition from insulin treatment to Sulfonylureas), were assessed 2 months after the change and 6 months after and the medication was removed 15 days before.
Results: Evolution HBA1c: 4.75%. Previous glucagon test: C-Peptide: 0: 0.22, 6: 0.82 ng/dl. At 2 months: 0.42. 6; 0.91ng/ml. Six months: 0: 0.27.6: 0.37 ng/ml. Previous GOTT: Insulin 0: 4, 120: 5.4 mU/ml. Glucose: 0: 230, 120: 298 m/dl. Two months: Glucose: 0: 80, 120: 238 mg/dl. Six months; Glucose: 0: 66, 120: 127 mg/dl.: Insulin: 0:3 and120: 2.8 mUI /ml. His mother had HBA1c: 6.5% wich decreased to 6% following commencement on sulfonyilureas. His grandmother had HBA1c: 10% wich similarly reduced to 6% following sulfonylureas treatment.
Conclusion: Clinical onset of diabetes in patients with mutations in ABCC8 gene in the first month of life are well documented. However, clinical picture can be different depending on the severity in the mutation as the case we present in the 3 family generations. Treatment with sulfonylureas improves the pancreatic reserve and metabolic control. Clinical follow-up of these patients is important, due to the risk of recurrence in 50% cases of DNT.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology