Neonatal Hyperinsulinemic Hypoglycemia Research Articles

Association of Fetal Catecholamines With Neonatal Hypoglycemia

Perinatal stress and fetal growth restriction increase the risk of neonatal hypoglycemia. The underlying pathomechanism is poorly understood. In a sheep model, elevated catecholamine concentrations were found to suppress intrauterine insulin secretion, followed by hyperresponsive insulin secretion once the adrenergic stimulus subsided. To determine whether neonates with risk factors for hypoglycemia have higher catecholamine concentrations in umbilical cord blood (UCB) and/or amniotic fluid (AF) and whether catecholamines are correlated with postnatal glycemia. In a prospective cohort study of 328 neonates at a tertiary perinatal center from September 2020 through May 2022 in which AF and UCB were collected immediately during and after delivery, catecholamines and metanephrines were analyzed using liquid chromatography with tandem mass spectrometry. Participants received postnatal blood glucose (BG) screenings. Risk factor for neonatal hypoglycemia. Comparison of catecholamine and metanephrine concentrations between at-risk neonates and control participants, and correlation of concentrations of catecholamines and metanephrines with the number and severity of postnatal hypoglycemic episodes. In this study of 328 neonates (234 in the risk group: median [IQR] gestational age, 270 [261-277] days; and 94 in the control group: median [IQR] gestational age, 273 [270-278] days), growth-restricted neonates showed increased UCB median (IQR) concentrations of norepinephrine (21.10 [9.15-42.33] vs 10.88 [5.78-18.03] nmol/L; P < .001), metanephrine (0.37 [0.13-1.36] vs 0.12 [0.08-0.28] nmol/L; P < .001), and 3-methoxytyramine (0.149 [0.098-0.208] vs 0.091 [0.063-0.149] nmol/L; P = .001). Neonates with perinatal stress had increased UCB median (IQR) concentrations of norepinephrine (22.55 [8.99-131.66] vs 10.88 [5.78-18.03] nmol/L; P = .001), normetanephrine (1.75 [1.16-4.93] vs 1.25 [0.86-2.56] nmol/L; P = .004), and 3-methoxytyramine (0.120 [0.085-0.228] vs 0.091 [0.063-0.149] nmol/L; P = .008) (P < .0083 was considered statistically significant). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were negatively correlated with AF C-peptide concentration (rs = -0.212, P = .005; rs = -0.182, P = .016; and rs = -0.183, P = .016, respectively [P < .017 was considered statistically significant]). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were positively correlated with the number of hypoglycemic episodes (BG concentration of 30-45 mg/dL) (rs = 0.146, P = .01; rs = 0.151, P = .009; and rs = 0.180, P = .002, respectively). Concentrations of UCB metanephrine and 3-methoxytyramine were negatively correlated with the lowest measured BG concentration (rs = -0.149, P = .01; and rs = -0.153, P = .008, respectively). Neonates at risk for hypoglycemia displayed increased catecholamine and metanephrine concentrations that were correlated with postnatal hypoglycemic episodes and lower BG levels; these results are consistent with findings in a sheep model that fetal catecholamines are associated with neonatal β-cell physiology and that perinatal stress or growth restriction is associated with subsequent neonatal hyperinsulinemic hypoglycemia. Improving the pathomechanistic understanding of neonatal hypoglycemia may help to guide management of newborns at risk for hypoglycemia.

Factors associated with neonatal hyperinsulinemic hypoglycemia, a case-control study.

We aimed to identify perinatal risk factors associated with hyperinsulinemic hypoglycemia in neonates. Secondary objectives included an examination of clinical and biochemical characteristics at the time of diagnosis and an exploration of the duration of diazoxide therapy. A case-control study was conducted, involving individual chart reviews of inborn infants diagnosed with hyperinsulinemic hypoglycemia (the HH group) between 2014 and 2021. These cases were paired with controls (the non-HH group) belonging to the same gestational age (GA) strata who did not exhibit HH or only had transient postnatal hypoglycemia. A total of 52 infants with HH were matched with corresponding controls. The mean GA in the HH group was 34.4±3.1weeks. Notably, the HH group exhibited lower mean minimum plasma glucose (PG) levels and required higher glucose infusion rates in comparison to the non-HH group (26.5±15.6 vs. 49.1±37.7 mg/dL and 12.9±3.8 vs. 5.7±2.1 mg/kg/min, respectively; p<0.001 for both). After adjusting for potential confounding factors, only two variables, fetal growth restriction (FGR) and neonatal sepsis, demonstrated significant associations with HH (adjusted odds ratio [95 % confidence interval]: 8.1 [2.1-31.0], p=0.002 and 6.3 [1.9-21.4], p=0.003, respectively). The median duration of diazoxide therapy for the HH group was 4months. FGR and neonatal sepsis emerged as notable risk factors for HH. These infants exhibited lower PG levels and necessitated higher glucose infusion rates compared to their non-HH counterparts. Importantly, a substantial proportion of the HH group received diazoxide therapy, with a median treatment duration of 4months.

Evaluation and management of neonatal onset hyperinsulinemic hypoglycemia: a single neonatal center experience

Objectives To evaluate the clinical characteristics and treatment options of neonates requiring prolonged hospitalization due to persistent hyperinsulinemic hypoglycemia (HH). Methods This retrospective cohort study included infants >34 weeks of gestation at birth who were born in our hospital between 2018 and 2021, diagnosed with HH, and required diazoxide within the first 28 days of life. The baseline clinical characteristics, age at the time of diagnosis and treatment options in diazoxide resistance cases were recorded. Genetic mutation analysis, if performed, was also included. Results A total of 32 infants diagnosed with neonatal HH were followed up. Among the cohort, 25 infants were classified as having transient form of HH and seven infants were classified as having congenital hyperinsulinemic hypoglycemia (CHI). Thirty-one percent of the infants had no risk factors. The median birth weight was significantly higher in the CHI group, whereas no differences were found in other baseline characteristics. Patients diagnosed with CHI required higher glucose infusion rate, higher doses, and longer duration of diazoxide treatment than those in the transient HH group. Eight patients were resistant to diazoxide, and six of them required treatment with octreotide and finally sirolimus. Sirolimus prevented the need of pancreatectomy in five of six patients without causing major side effects. Homozygous mutations in the ABCC8 gene were found in four patients with CHI. Conclusions The risk of persistent neonatal hyperinsulinism should be considered in hypoglycemic neonates particularly located in regions with high rates of consanguinity. Our study demonstrated sirolimus as an effective treatment option in avoiding pancreatectomy in severe cases.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation

BackgroundPersistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.Patient presentationWe report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.ConclusionsKabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

Diazoxide use for neonatal hyperinsulinaemic hypoglycaemia in a low-resource setting: A Case Report

The management of neonatal hyperinsulinaemic hypoglycaemia remains a major challenge in hospitalized newborns globally. Diazoxide is one of the recommended therapeutic options. We report a late preterm, male infant of a diabetic mother who suffered severe perinatal asphyxia and had persistent hypoglycaemia requiring progressively increasing intravenous glucose concentrations to as high as 12.5 mg/kg/minute along with intravenous hydrocortisone administration. A critical sample revealed inappropriately high serum insulin, inappropriately low serum cortisol and growth hormone responses. Urinalysis was negative for ketones. With the persistence of hypoglycaemia, oral diazoxide at 5 mg/kg/day with oral hydrochlorothiazide was administered. The infant was diazoxide-responsive with complete resolution of hypoglycaemia. Diazoxide therapy was discontinued after 14 days and he was discharged after one month of admission. This report emphasizes the importance of diazoxide in the management of neonatal transient hyperinsulinaemic hypoglycaemia. The availability and cost of diazoxide, as well as the endocrine and metabolic tests, are major concerns in resource-poor settings.

The effect of hypoglycaemia on neurocognitive outcome in children and adolescents with transient or persistent congenital hyperinsulinism.

To examine the hypoglycaemic effect on neurodevelopmental outcome in patients with transient and persistent congenital hyperinsulinism (CHI) born in the 21st century. A cohort of 117 patients (66 males, 51 females) with CHI aged 5 to 16years (mean age 8y 11mo, SD 2y 7mo) were selected from a Finnish nationwide registry to examine all the patients with similar methods. Neurodevelopment was first evaluated retrospectively. The 83 patients with no risk factors for neurological impairment other than hypoglycaemia were recruited and 44 participated (24 males, 20 females; mean age 9y 7mo, SD 3y 1mo) in neuropsychological assessment with the Wechsler Intelligence Scale for Children, Fourth Edition and the Finnish version of the Developmental Neuropsychological Assessment, Second Edition domains of attention, language, memory, sensorimotor, and visual functioning. In retrospective analysis, transient and persistent CHI groups had similar prevalences of mild (22% and 18% respectively) or severe (5% and 7% respectively) neurodevelopmental difficulties. In clinical assessment, the neurocognitive profile was within the average range in both groups, but children with persistent CHI showed significant but restricted deficits in attention, memory, visual, and sensorimotor functions compared with the general population. The transient CHI group did not differ from the standardization samples. Besides the more apparent broader neurological deficits, children with persistent CHI have an increased risk for milder specific neurocognitive problems, which should be considered in the follow-up. Children with persistent congenital hyperinsulinism showed deficits in attention, memory, visual, and sensorimotor functions. The deficits were potentially of hypoglycaemic origin. Children with transient hyperinsulinism did not differ from the general population.

Transient neonatal hyperinsulinaemic hypoglycaemia: perinatal predictors of length and cost of stay.

Admission to neonatal care causes separation of infants from their parents, can adversely affect breast-feeding and is associated with painful procedures. Our aim was to identify perinatal factors and cost of care associated with transient neonatal hyperinsulinaemic hypoglycaemia (HH). Infants born after 35weeks of gestation admitted because of hypoglycaemia were studied. The neonates were divided into two groups (HH and non-HH), and their length and cost of care were compared and perinatal factors predicting those outcomes explored. Forty of the 474 infants admitted with hypoglycaemia were diagnosed with HH. The HH group had a lower median (IQR) glucose level on admission compared to the non-HH group (p< 0.001). The median (IQR) cost of stay was higher in the HH group (p< 0.001). In the HH group, the GIRmax was significantly correlated with cost of stay (p< 0.001). GIRmax predicted a cost of stay >£9140 with an area under the ROC curve of 0.956. GIRmax> 13.9mg/kg/min predicted admission cost >£9140 with 86% sensitivity and 93% specificity.Conclusion: Transient neonatal HH was associated with a higher length and cost of stay in infants admitted for hypoglycaemia. The GIRmax can predict the length and cost of stay. What is Known: • Neonatal hypoglycaemia is the leading cause of term and late preterm neonatal admissions. • Hyperinsulinism (HH) is the commonest cause of persistent hypoglycaemia, and delay in the diagnosis and management can have a detrimental impact on long-term development. What is New: • We have demonstrated prior to NICU admission that blood glucose concentrations were lower in infants with HH compared to those without. • The maximum GIR had a stronger correlation with total length and cost of hospital stay compared to insulin levels in HH infants.

An Atypical HNF4A Mutation Which Does Not Conform to the Classic Presentation of HNF4A-MODY

Objective To present the case of an atypical Hepatocyte Nuclear Factor 4 Alpha (HNF4A) mutation that is not consistent with the classically published presentation of HNF4A-Mature Onset Diabetes of the Young (MODY). Methods Clinical presentation and literature review. Results A 43-year-old nonobese man was referred to the endocrinology clinic for evaluation of elevated fasting blood glucose (FBG) measurements. Laboratory review revealed prediabetes and hypertriglyceridemia for the previous decade. Testing of autoantibodies for type 1 diabetes was negative. Genetic testing showed an autosomal dominant, heterozygous missense mutation (c.991C>T; p.Arg331Cys) in the HNF4A gene, which is correlated with HNF4A-MODY. Phenotypically, patients with an HNF4A-MODY tend to have early-onset diabetes, microvascular complications, low triglyceride levels, increased birth weight, fetal macrosomia, and less commonly neonatal hyperinsulinemic hypoglycemia. The patient did not demonstrate any of these features but instead presented with late-onset diabetes, an elevated triglyceride level, and a normal birth weight. Conclusion Our patient likely represents an atypical variant of HNF4A-MODY with a milder clinical presentation. Patients with atypical, less-severe presentations of HNF4A-MODY may be largely undiagnosed or misdiagnosed, but identification is important due to implications for treatment, pregnancy, and screening of family members.

Neonatal hyperinsulinemic hypoglycemia in a patient with 9p deletion syndrome

We report the clinical and neuroradiological findings in a young boy harboring the 9p deletion syndrome including the novel findings of thalamic infarction and germinal matrix haemorrhage and neonatal hyperinsulinemic hypoglycemia. Both the hypoglycemic events and the ventriculomegaly found in this patient have previously only been reported in two patients, while the thalamic infarction and germinal matrix haemorrhage are novel features.

Regulation of KATP Channel Trafficking in Pancreatic β-Cells by Protein Histidine Phosphorylation.

Protein histidine phosphatase 1 (PHPT-1) is an evolutionarily conserved 14-kDa protein that dephosphorylates phosphohistidine. PHPT-1-/- mice were generated to gain insight into the role of PHPT-1 and histidine phosphorylation/dephosphorylation in mammalian biology. PHPT-1-/- mice exhibited neonatal hyperinsulinemic hypoglycemia due to impaired trafficking of KATP channels to the plasma membrane in pancreatic β-cells in response to low glucose and leptin and resembled patients with congenital hyperinsulinism (CHI). The defect in KATP channel trafficking in PHPT-1-/- β-cells was due to the failure of PHPT-1 to directly activate transient receptor potential channel 4 (TRPC4), resulting in decreased Ca2+ influx and impaired downstream activation of AMPK. Thus, these studies demonstrate a critical role for PHPT-1 in normal pancreatic β-cell function and raise the possibility that mutations in PHPT-1 and/or TRPC4 may account for yet to be defined cases of CHI.

The Genetic Architecture of Diabetes in Pregnancy: Implications for Clinical Practice.

The genetic architecture of diabetes mellitus in general and in pregnancy is complex, owing to the multiple types of diabetes that comprise both complex/polygenic forms and monogenic (largely caused by a mutation in a single gene) forms such as maturity-onset diabetes of the young (MODY). Type 1 diabetes (T1D) and type 2 diabetes (T2D) have complex genetic etiologies, with over 40 and 90 genes/loci, respectively, implicated that interact with environmental/lifestyle factors. The genetic etiology of gestational diabetes mellitus has largely been found to overlap that of T2D. Genetic testing for complex forms of diabetes is not currently useful clinically, but genetic testing for monogenic forms, particularly MODY, has important utility for determining treatment, managing risk in family members, and pregnancy management. In particular, diagnosing MODY2, caused by GCK mutations, indicates that insulin should not be used, including during pregnancy, with the possible exception of an unaffected pregnancy during the third trimester to prevent macrosomia. A relatively simple method for identifying women with MODY2 has been piloted. MODY1, caused by HNF4A mutations, can paradoxically cause neonatal hyperinsulinemic hypoglycemia and macrosomia, indicating that detecting these cases is also clinically important. Diagnosing all MODY types provides opportunities for diagnosing other family members.

Second Arab Society for Pediatric Endocrinology and Diabetes Conference, 6th-8th November 2014, Abu Dhabi, United Arab Emirates

The scientific program of the conference featured 62 oral and 84 poster presentations. Diabetes was the topic most heavily presented due to its widespread prevalence and unique features in our region. Milestones in diabetes care, diabetes education, epidemiology, updates in neonatal diabetes and hyperinsulinemic hypoglycemia as well as insulin resistance and type 2 diabetes mellitus were among the topics discussed by leading world-renown authorities as well as by regional experts. Diabetes technology was a particularly hot topic in the meeting featuring 2 symposia on the recent advances in artificial pancreas and regional experience with insulin pumps and continuous glucose monitoring systems. Experience pertinent to diabetes and fasting was elegantly presented by regional experts. The meeting also featured workshops dedicated to diabetes educators and stimulating discussions with behavioral psychologists. Growth disorders were presented in different formats of plenary, “Meet the Expert”, multicenter research study presentation, case presentations. Surveillance of growth hormone use was presented from Tunisia and Kuwait. In addition, pubertal disorders were widely covered. Speakers highlighted regional trends in precocious puberty, updates on PCOS management, adrenal disorders and novel mutations in a variety of puberty-related disorders. Exciting data regarding survivors of childhood cancer as well as updates in Turner syndrome management were brilliantly presented. A session of particular interest tackled disorders of sexual differentiation (DSDs), starting with an overview of medical approach to DSDs, followed by an animated presentation and discussion of religion point of view regarding DSDs as well as a valuable psychological approach to youth with DSDs and their families. Last but not least, a highly informative session was held on bone disorders and vitamin D status in the region.

Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha and 4 Alpha in Maturity-Onset Diabetes of the Young and Hyperinsulinemic Hypoglycemia

Maturity-onset diabetes of the young (MODY) is a monogenic disorder characterized by autosomal dominant inheritance of young-onset (typically <25 years), noninsulin-dependent diabetes due to defective insulin secretion. MODY is both clinically and genetically heterogeneous with mutations in at least 10 genes. Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations studied. The number of different pathogenic HNF1A mutations totals 414 in 1,247 families. Mutations in the HNF4A gene encoding hepatocyte nuclear factor-4 alpha are a rarer cause of MODY with 103 different mutations reported in 173 families to date. Sensitivity to treatment with sulfonylurea tablets is a feature of both HNF1A and HNF4A mutations. The HNF4A MODY phenotype has been expanded by the reports of macrosomia in ∼50% of babies, and more rarely, neonatal hyperinsulinemic hypoglycemia. The identification of an HNF1A or HNF4A gene mutation has important implications for clinical management in diabetes and pregnancy, but MODY is significantly underdiagnosed. Current research is focused on identifying biomarkers and developing probability models to identify those patients most likely to have MODY, until next generation sequencing technology enables cost-effective gene analysis for all patients with young onset diabetes.

1641 Diazoxide Opens the Closing Neonatal Ductus Arteriosus

Background and AimsSulfonylureas inhibit the ATP-sensitive potassium (KATP) channel, are insulinogenic, and close the fetal ductus arteriosus. Diazoxide, a KATP channel opener, is used for neonatal hyperinsulinemic hypoglycemia, and has...

Hepatocyte Nuclear Factor 4α Gene Mutation Associated with Familial Neonatal Hyperinsulinism and Maturity-Onset Diabetes of the Young

Neonatal macrosomia and hyperinsulinemic hypoglycemia with strong family history of diabetes may indicate monogenic diabetes. Here we report a family in which 4 individuals in 3 generations were found to have a mutation (Arg80Gln) in hepatocyte nuclear factor 4α. Genetic testing was a factor in choosing sulfonylurea therapy for diabetes.

Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell

Recessive mutations in ABCC8/KCNJ11 of beta-cell K(ATP) channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited K(ATP) channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive K(ATP) channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.

The Clinical Problem of Hyperinsulinemic Hypoglycemia and Resultant Infantile Spasms

Hyperinsulinemic hypoglycemia (HH) is a cause of severe hypoglycemia in the newborn and infancy period and is associated with a high risk of neurologic handicap and epilepsy. Infantile spasms after exposure to HH is rare and has been described in only 1 previous report. We report the clinical, biochemical, and neurodevelopmental characteristics of 5 patients with neonatal-onset HH who subsequently developed infantile spasms. All 5 patients had neonatal-onset HH of varying severity and duration. These patients presented with the characteristic ictal pattern of spasms in clusters at a mean age of 6.6 months. Characteristic hypsarrhythmia was noted in only 3 of 5 patients. Structural abnormality was found in only 1 of 4 patients who underwent MRI of the brain. Infantile spasms responded to medical treatment in 3 patients, spasms in 1 patient were refractory to antiepileptic drugs, and treatment duration was insufficient for us to comment on the response in 1 patient. Developmental delay was evident in all of them. In conclusion neonatal HH of varying severity is associated with later (after a latent period) development of infantile spasms. The latent period before the onset of the spasms can be variable; hence, long-term neurodevelopmental follow-up (until 1 year of age) is necessary.

Neonatal hyperinsulinaemic hypoglycaemia and monogenic diabetes due to a heterozygous mutation of the HNF4A gene

Recent research has demonstrated that mutations of the hepatocyte nuclear factor 4-alpha (HNF4A) gene are associated with neonatal hyperinsulinaemic hypoglycaemia. Mutations of this gene also cause one of the subtypes of monogenic diabetes, a form of diabetes formerly known as maturity-onset diabetes of the young. This article describes a family discovered to have a novel frame-shift mutation of the HNF4A gene in the setting of early-onset maternal diabetes and severe neonatal hyperinsulinaemic hypoglycaemia. The implications of a diagnosis of HNF4A gene mutation for obstetric and paediatric practice are discussed.

Long-term MRI findings of a case with persistent hyperinsulinemic hypoglycemia of infancy (nesidioblastosis)

Background and purpose To describe the sequential magnetic resonance imaging (MRI) findings in a neurologically handicapped newborn who had been suffered from neonatal hypoglycemia due to persistent hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) and to evaluate the following changes in the long-term radiological follow-up. Case A case of newborn with severe hypoglycemia due to nesidioblastosis is reported. The patient was presented with poor feeding, irritability, and seizures. Nesidioblastosis was diagnosed on the basis of high intravenous glucose requirement, high insulin to glucose ratio, negative urinary ketones. Normoglycemia was maintained by a combined treatment including glucose infusions and steroid, and then somatostatin analoques. The patient was assessed neurologically and radiologically by sequential cerebral MRI within 2 years follow-up. Results The most striking findings were cystic lesions on corona radiata, parietooccipital deep white matter and diffuse subcortical involvement of the brain at the initial MRI. The lesions were recovered radiologically at the 5 months of age. Diffuse hyperintensity of the periventricular white matter and optic radiation suggests abnormal and delayed myelination at 1 year of age, and periventricular leukomalacia and ventricular irregularity at 2 years of age. More delayed neurologic sequelae included mental retardation and spasticity. Conclusion Neonatal hyperinsulinemic hypoglycemia must be suddenly and appropriately diagnosed and treated to prevent any further neurological dysfunction and damage. MRI studies are crucial in nesidioblastosis to define the characteristics and severity of cerebral lesions after hypoglycemia. Long-term radiologic follow-up should be further investigated to predict the neurologic outcome, although the radiologic recovery period was seen in acute or subacute phase of the disease.