Abstract
Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystemic disorder characterized by an increased risk of benign and malignant tumor formation affecting skin, bone and nervous system. In children with NF1, endocrine manifestations include central precocious puberty, growth hormone deficiency and growth hormone hypersecretion, resulting from complications of optic pathway gliomas involving the hypothalamic and sellar region. A few reports of adults with NF1 have been described to have hypoglycemia due to insulinoma. However, hypoglycemia due to hyperinsulinism has not been described in children with NF1. We present a case of NF1 diagnosed during neonatal period associated with congenital hyperinsulinism.
Case: Patient was delivered at 36 weeks by C- section with birthweight of 2780 grams which was appropriate for her gestational age. There was no maternal history of diabetes. Pertinent exam findings included microcephaly and multiple café-au-lait spots. She developed hypoglycemia at DOL1 with blood glucose of 26 mg/dl which normalized with IV dextrose at a glucose infusion rate of 6 mg/kg/min. At DOL8, an attempt to wean IV dextrose failed and she developed hypoglycemia with blood glucose of 47 mg/dl. Critical sample showed insulin level 3.3 uU/ml, betahydroxybutyrate 0.08 mg/dl (0.2-2.8), cortisol 18.1 mcg/dL and GH 13.2 ng/mL. A glucagon stimulation test showed an increase in glucose of 30 mg/dl. She was diagnosed with hyperinsulinism and started on Diazoxide (8 mg/kg/day) with improvement of blood glucose with prefeed glucose of > 70 mg/dl. She had normal 8- hour fasting tolerance with all BG > 70 while on Diazoxide. Genetic test for known mutations causing hyperinsulinism was negative. Microarray confirmed a 1.42Mb interstitial deletion at chromosome 17q11.2 which encompasses NF1 gene confirming the diagnosis of NF1. Additionally, she has an Xp22.33 duplication of uncertain clinical significance.
Conclusion: Our patient presented with an unusual association between congenital hyperinsulinism and NF1. Further testing needs to be performed to determine whether this association is coincidental or whether congenital hyperinsulinism is a rare manifestation of NF1.
Neovascular Glaucoma Induced by Peripheral Retinal Ischemia in Neurofibromatosis Type 1: Management and Imaging Features