Successful Transition to Oral Glyburide in a Patient with Neonatal Diabetes, Developmental Delay and Seizures (DEND Syndrome) due to KCJN11 mutation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 596-623-Case Reports: Pediatric Endocrinology & Metabolism
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-611
Susan P Almazan*1 and Maria D Urban2
1Childrens Med Ctr of Dayton, Beavercreek, OH, 2na, Dayton, OH

Activating mutation in the KCJN11 gene is the cause of 30-50% of  permanent neonatal diabetes. Besides having neonatal diabetes,  some patients with  this mutation also manifest  with developmental delays and epilepsy, thus designated to have DEND syndrome.  This case presents a patient with DEND and his successful transition from insulin therapy to oral glyburide.

 Clinical Case:

Patient  is an  African American male, a product of 39 weeks gestation complicated by gestational diabetes.   He was delivered  by CS for fetal heart deceleration.  Birthweight was 2582 grams (3%).  At 3 months of age, he presented in DKA , with hemoglobin A1c  of  13.7%, C-peptide  of  < 0.5  (0.8-3.5 ng/ml) ,  and  negative insulin and  islet cell antibodies.  Patient was  initially maintained on subcutaneous injections of NPH  and aspart insulin. At 6 months of age, therapy was changed to insulin pump due to multiple episodes of hypoglycemia.  Developmental  delay was noted by 6 months of age.  At  2 years of age, he was found to be  heterozygous for a missense mutation (R50P)in the KCNJ11 gene (genetic study performed by  Dr. Andrew Hattersley’s laboratory) .  Both parents  were  negative for this mutation.  At 2 10/12 years of age, patient was admitted for transitioning to oral glyburide( Dr. Hattersley’s protocol).  Attempt to transition was discontinued when he developed ketosis. 

 At 6 years of age, he was still unable to stand alone.  He did not speak any meaningful word but made random sounds.  At this age, he had several  episodes of tonic clonic seizures.  After evaluation by neurology service  and documentation of  abnormal EEG, patient was started on antiseizure medication.

At 6 6/12 years of age, he was admitted again  for transitioning to oral glyburide.  Glyburide was  initially started  at  0.1 mg/kg/day  and dose  was gradually increased while insulin dose was correspondingly tapered down.  Except for transient diarrhea and vomiting when glyburide was started, patient exhibited no other  side effects. No further  seizures  occurred up to the present.  Patient started to walk with slow broad based gait three months after glyburide therapy was initiated.  

Patient was completely off insulin therapy six months after initiation of oral glyburide.  Current dose of glyburide is  at 1.9 mg/kg/day.  Prior to transitioning to glyburide, hemoglobin A1c was 9% and C-peptide was < 1 ng/ml.  At 14 months after transitioning to glyburide, hemoglobin A1c  was  6.4 % and C-peptide level  was 1.1 ng/ml.  


This case illustrates that oral  glyburide is an effective therapy for glycemic control in this patient with DEND due to KCNJ11 mutation.  It also emphasizes  the importance of testing for this mutation in patients  presenting with neonatal diabetes .



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