ESPE Abstracts

Background: Neonatal Diabetes Mellitus (NDM) is a rare monogenic disease with an incidence of 1/21000-300 000 live births, increasing with consanguinity. NDM presents with hyperglycemia from the 1^st few days till 6 months of life. Few cases start between 6 to 12 months or later. NDM is divided into transient (TNDM) and permanent (PNDM). TNDM type 1 is caused by mutation at 6q24 whereas TNDM type 2 is mainly caused by mutation in K-ATP channel genes ABCC8 or KCNJ11 and represents 50-60% of NDM.

Case: We reported a 50-day-old-male born at term by caesarian section to a 24 year-old G2P2A0 woman presented for low grade fever, severe dehydration, lethargy, diaper full of urine with no dysmorphism. Laboratory analysis showed glucosuria, hyperglycemia 1640 mg/dl, normal HbA1c 5%, low insulinemia and C peptide. He had a birth weight of 2.660g and length 47cm without a family history of NDM. Atrial-septal-defect was seen on cardiac ultrasound and venous sinus thrombosis on brain MRI. Genetic analysis of the boy and his parents showed a de novo heterozygous activating mutation of ABCC8 gene NM-001287174.1:C.4567 G>Ap.(Val1523 Met) which altered the ability of SUR1 subunit of K-ATP channels to respond to ATP/ADP changes leading them to remain open, preventing the membrane depolarization, calcium entry and insulin release. After resuscitation with fluids, electrolytes, low insulin infusion. A decrease in insulin need was seen over 3 months until cessation without necessity of sulfonylurea administration.

Discussion: Neonatal hyperglycemia is a common metabolic disorder in neonatal period. Many etiologies exist such as sepsis, stress, glucose infusion, glucocorticoid, and catecholamine utilization. NDM should be raised with a family history of NDM, intrauterine growth retardation, poor weight gain, dehydration with excessive urine, presence of dysmorphism, cardiac murmur, macroglossia and umbilical hernia. HbA1c couldn’t be used as marker of glycemia status because of the rapidity of onset and the presence of fetal hemoglobin. Insulinemia, C-peptide level, islet cell, insulin, GAD, ZnT8 antibodies levels should be done to eliminate autoimmune DM. Ultrasound of heart, kidney and thyroid should be done for possible associated malformations. Genetic study is important for the diagnosis, management and prognosis of patient.

Conclusion: Our objective was to familiarize pediatricians about the presence of NDM in a full term newborn with intrauterine growth retardation, low grade fever, severe dehydration and excessive diuresis. TNDM2 presents later (4-20 weeks), remits later (35 weeks) and relapses earlier (4.7years) than TNDM1 as in our case.