The proband was the firstborn male from an IVF dichorionic twin pregnancy born by spontaneous vaginal delivery at 37 weeks gestational age weighing 1984 g (-2.53 SDS) to healthy consanguineous parents (first cousins) of Arab-Muslim origin. No family history of diabetes was reported in the extended family. The newborn was admitted to the neonatal intensive care unit (NICU) due to low birth weight. In the first 24 h, he had low blood pressure that was treated with intravenous glucose 10%. On examination, no dysmorphic features were observed. Elevated blood glucose levels were observed during the first 24 h of life and through the first 5 days of life (range 61-443 mg/dL). The patient was treated with total parenteral nutrition for the first 4 days and was switched to milk formula at 5 days of age. He was treated intravenously with regular insulin from day 5 of life at a daily dose of 0.24-1.2 U/kg, which was replaced by a combination of subcutaneously injected diluted Humalog  (insulin lispro) twice daily at a dose of 0.03-0.05 U before meals, and NPH insulin once or twice daily at a dose of 0.2-0.4 U/kg. Due to labile blood glucose levels, treatment with a continuous subcutaneous insulin infusion (CSII) pump (MiniMed 640G SmartGuard  system) was initiated at 2 weeks of age. The infant weighed 1730 g. A MMT399 QuickSet Infusion Set was inserted into the upper lateral part of the buttocks. Regular insulin was administered at a basal rate of 0.3-0.6 U/kg per day with 2-3 boluses of 0.025 U each. The SmartGuard system offers protection against hypoglycemia by automatically stopping insulin instillation when the glucose sensor approaches a predefined lower limit. Maintaining stable blood glucose levels was very challenging due to fluctuating hyperglycemia and hypoglycemia (glucose levels ranged between 50 and 500 mg/dL). Hypoglycemic episodes were noted even after a few hours of insulin withdrawal, whereas low insulin-delivery rates resulted in pump obstruction, causing hyperglycemia. CSII using Humalog diluted 1:10 (10 U/mL) with continuous glucose monitoring (CGM) maintained blood glucose within 100-250 mg/dL, but the pump frequently shut down due to decreasing sensor glucose levels, on some days for more than 6 h ( Figure 1 ). Laboratory assessment revealed very low levels of insulin (less than 0.2 microIU/mL; normal range 3.0-25.0), 0.1 ng/mL C-peptide (normal range 1.1-5.0) and negative anti-pancreatic antibodies ( Table 1 ).
Thyroid function testing during the first week of life revealed primary CH with thyroid-stimulating hormone (TSH) above 150 microIU/mL (normal range 0.64-6.27), free thyroxine (FT4) less than 1.3 pmol/L (normal range 11.4-19.0) and free triiodothyronine of 1.99 pmol/L (normal range 3.5-6.5). Thyroxine (L-T4) therapy was started at a dose of 15 microg/kg per day, which maintained thyroid function within the normal range after 2 weeks. During the follow-up period, his FT4 and TSH levels were within normal ranges or slightly elevated. Thyroid sonography demonstrated a normally sized non-ectopic thyroid gland.
Corneal opacity was noted early in the course of neonatal care and bilateral CG was diagnosed. Bilateral eye trabeculotomy was performed at 6 weeks of age. Repeat eye surgery was performed at 18 months of age due to increased intraocular pressure.
Renal sonography showed normally sized echogenic kidneys with small cortical cysts, mainly around the pyramids. Blood pressure and renal function tests were normal. Repeated renal sonography at the age of 3 years showed normally sized kidneys with small echogenic foci and small 4 mm cysts.