neonatal hypoglycemia is caused by numerous clinical conditions , such as birth asphyxia , small for gestational age ( sga ) , premature birth , and infants born to diabetic mothers , systemic disorders , hormonal disorders or fatty acid oxidation disorders . of them , infants that experience birth asphyxia , sga , premature birth , and born to diabetic mothers usually have transient hyperinsulinism that resolves quickly , even though it may be quite severe1 ) . however , persistent hypoglycemia can be caused by hyperinsulinism , even if there is no history or biochemical evidence of maternal diabetes , birth asphyxia , premature birth or sga . congenital hyperinsulinism ( chi or persistent hyperinsulinemic hypoglycemia of infancy ; omim#256450 ) is the most common cause of nonketotic persistent severe hypoglycemia in neonates and caused by inappropriate insulin secretion from pancreatic  cells23 ) . inherited or sporadic mutations in the regulation of the potassium channel involved in insulin secretion by the pancreatic  cells can lead to chi1 ) . the most common causes of chi are mutations that inactivate the abcc8 and kcnj11 genes encoding the sulfonylurea receptor 1 ( sur1 ) and the inward rectifying potassium channel ( kir6.2 ) subunit of the atp - sensitive potassium channel4 ) . it is rare but critical condition that occurs during the neonatal period and is accompanied by hypoglycemia . persistent hypoglycemia is a major risk factor for mental retardation , therefore , early diagnosis and treatment are extremely important25 ) . recently , we examined a baby with diazoxide unresponsive chi with a novel mutation in the abcc8 gene and would like to report our case in this paper . a 2-day - old girl was transferred to our hospital with repetitive myoclonic movements and apnea . she was born at 41 weeks of gestation and her birth weight was 4.1 kg ( 90th97th percentile ) . father denied any perinatal problems such as gestational diabetes mellitus , prolonged rupture of membrane , polyhydramnios or oligohydramnios . the patient was delivered vaginally and her apgar scores were 9 at 1 minute and 10 at 5 minutes after birth , respectively . she was transferred to our hospital at 2 days of age because she presented frequent myoclonic movements of the upper and lower limbs and oxygen desturation around 70% after birth . on admission , blood pressure was 69/41 mmhg , heart rate was 158 beats per minute , respiration rate was 50 breaths per minute and body temperature was 36.7. weight was 3.8 kg ( 75th90th percentile ) , length was 53.5 cm ( 90 - 95 percentile ) , head circumference was 34 cm ( 25th50th percentile ) , chest circumference was 34.5 cm , and abdominal circumference was 35 cm . she was lethargic and presented with hypotonic posture . upon physical examination , she showed clear breathing sounds , regular heart beat and no cardiac murmur . after she was admitted , she displayed repetitive myoclonic movements of upper and lower limbs , apnea and oxygen desaturation . a blood sugar test ( bst ) was performed immediately and the result was 18 mg / dl . eight milliliters of 10% dextrose solution was injected as a bolus and 10% dextrose solution was continuously infused with a glucose infusion rate ( gir ) of 4.07 mg / kg / min . the gir was increased up to 20.8 mg / kg / min steadily and bood sugar was elevated to 95 mg / dl . after the blood sugar level reached a normal range , she stopped experiencing myoclonic seizure and apnea . initial blood work showed a hemoglobin of 18.4 g / dl , hematocrit of 55% , a white blood cell count of 24,830/mm , and a platelet count of 283,000/mm . serum blood glucose was 2 mg / dl on initial chemistry and the bst revealed a blood glucose of 18 mg / dl . serum calcium was 8.8 mg / dl , bicarbonate was 19 mmol / l , and ammonia was 69 g / dl ( reference range , 1987 g / dl ) . c - reactive protein was 4.6 mg / dl ( reference range , 05 mg / dl ) and no bacterial growth was noted on blood culture . miu / l ( reference range , 2.025.0 miu / l ) , and c - peptide was 5.96 ng / ml ( reference range , 1.14.4 ng / ml ) when serum glucose level was 13 mg / dl . chest x - ray showed no ground glass opacity . on the second day in the hospital , brain magnetic resonance image with diffusion was performed because of repetitive seizures and apnea . high signal intense lesions in left parietal lobe , both occipital cortices , and subcortical white matter were observed ( fig stay , abdominal ultrasonography was performed to determine the presence of any pancreatic lesions such as adenoma , but no pancreatic problems could be detected . electroencephalogram showed some attenuation of the background and an echocardiogram showed a hypertrophied interventricular septum ( 5.9 mm , > 97th percentile ) and a left ventricular posterior wall ( 45 mm , upper normal limit ) without obstruction of the left ventricular outflow tract . computed tomography and positron emission tomography of the pancreas were not performed because of the risk of radiation exposure . we fed her using levin tube because she could not suck and swallow milk well on the 1st day of admission . when feeding volume reached to 150 ml / kg , blood glucose levels fluctuated between 31 to 162 mg / dl under the high intravenous gir of 11.0616.57 mg / kg / min . however , blood glucose was still fluctuated with 20 mg / kg / day of diazoxide , so we added octreotide subcutaneously 21 days after being admitted ( fig . full sequencing of the abcc8 gene was performed because abcc8 mutation is more prevalent than kcnj11 in korea2 ) . genetic analysis revealed a new heterozygotic variation of c.4608g > a on exon 38 of abcc8 ( fig . after the genetic diagnosis , father wanted her to be transferred to other hospital when she was 24 days old . at that time , blood glucose was still fluctuating even though she was receiving diazoxide and octretide injections . she has not visited our hospital after discharge , but we received a report on her clinical condition from a relative in korea 3 years later . up to now , there have been many nation - wide studies about abcc8 and kcnj11 mutations in patients with chi3678 ) and more than 150 mutations have been reported in the abcc8 gene9 ) . twelve different mutations of the abcc8 gene have been reported in korean patients2 ) . here we report on a new mutation in the abcc8 gene , a single base alteration at a position 4608 ( 4608g > a ) on exon 38 . the alteration was neither identified in the polymorphism and mutation database until now ( http://www.ncbi.nlm.nih.gov/snp ) . the site of the new alteration is the last base sequence of exon 38 in the abcc8 gene and might affect exon - intron splicing . the human abcc8 gene located on chromosome 11p15.1 has 39 exons and encodes the 1581 amino acids of the sur1 protein . the sur1 protein is one subunit of the atp sensitive katp channels in pancreatic  cells . the pancreatic katp channel plays a major role in regulating insulin secretion from the  cell . a defective or inactivated pancreatic katp channel can cause hyperinsulinemia despite hypoglycemia10 ) . to diagnose hyperinsulinemic hypoglycemia , clinicians rely on clinical and laboratory findings at the moment of hypoglycemia . hyperinsulinemia can be supported by inappropriately high insulin concentrations accompanied by hypoglycemia , low or no fatty acids and ketone bodies , a glycemic response to glucagon injection and a high gir to maintain euglycemia11 ) . in our case , chi was diagnosed based on gir of 20.8 mg / kg / min required to maintain euglycemia , 9.1 miu / l of insulin and no ketone bodies with a serum glucose level of 13 mg / dl , and low level of free fatty acids . the goal of chi treatment is to preventing brain damage , however , it is one of the most difficult diseases to manage . diazoxide is a benzothiazine derivative that acts on the sur1 subunit of the katp channel . nifedipine is a calcium channel blocker and has been reported as effective drug in regulating insulin secretion1213 ) . when chi patients fail to respond to medical and nutritional treatment , a pancreatectomy should be considered . however , as pancreatectomy has several risks including the inherent risks of surgery , persistent hypoglycemia and risk of developing diabetes mellitus postoperatively5 ) , so surgery is carefully considered . in this case , serum glucose levels fluctuated in spite of a gir of 20.8 mg / kg / min and enteral feeding . we tried corticosteroids , diazoxide and octreotide , but those were ineffective in maintaining normal blood glucose levels . although treatment of chi is primarily based on the use of diazoxide , chi caused by recessive inactivating mutations in the abcc8 and kcnj11 genes is usually unresponsive to medical treatment with diazoxide10 ) . after being transferred to another hospital , we heard that she slowly responded to medical managements over a period of 2 months and she finally could be taken off diazoxide and octreotid at around 3 months of age . we cautiously hypothesize that it is possible that she experienced spontaneous remission of chi . according to previous reports apoptotic death of insulin - oversecreting  cells and functional shutdown of insulin secretion were suggested as possible mechanisms for the spontaneous remission of chi11 ) . though only a single base was altered , c.4608g > a on exon 38 of abcc8 in this case might be a possible cause of chi , along with her symptoms and laboratory findings . the genetic of chi is known as recessive trait , however , the single alteration of our case might be overdominant15 ) . functional studies and genetic analyses of parents are necessary to confirm . in the aspect of neurologic complication of seizure disorder in this patient , early diagnosis and aggressive nutritional and medical management
congenital hyperinsulinism ( chi ) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia . 
 hypoglycemia in chi occurs secondary to the dysregulation of insulin secretion . 
 chi has been established as a genetic disorder of islet - cell hyperplasia , associated with a mutation of the abcc8 or kcnj11 genes , which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel ( kir6.2 ) subunit of the atp - sensitive potassium channel , respectively . 
 we report the case of a female newborn infant who presented with repetitive seizures and episodes of apnea after birth , because of hypoglycemia . 
 investigations revealed hypoglycemia with hyperinsulinemia , but no ketone bodies , and a low level of free fatty acids . 
 high dose glucose infusion , enteral feeding , and medications could not maintain the patient 's serum glucose level . 
 genetic testing revealed a new variation of abcc8 mutation . 
 therefore , we report this case of chi caused by a novel mutation of abcc8 in a half - korean newborn infant with diazoxide - unresponsive hyperinsulinemic hypoglycemia .