Volume 29, Issue 3

Nutrition during prenatal, early postnatal and pubertal period is crucial for the development of insulin resistance and its consequences. During prenatal period fetal environment and nutrition seems to interfere with metabolism programming later in life. The type of dietary carbohydrates, glycemic index, protein, fat and micronutrient content in maternal nutrition could influence insulin sensitivity in the newborn. The effects of lactation on metabolism and nutritional behavior later in life have been studied. Dietary habits and quality of diet during puberty could prevent the onset of a pathological insulin resistance through an adequate distribution of macro- and micronutrients, a diet rich in fibers and vegetables and poor in saturated fats, proteins and sugars. We want to overview the latest evidences on the risk of insulin resistance later in life due to both nutritional behaviors and components during the aforementioned periods of life, following a chronological outline from fetal development to adolescence.

Background: Raising the awareness of childhood diabetes symptoms can reduce the frequency of diabetic ketoacidosis (DKA) at onset of type 1 diabetes (T1D). However, data on the effectiveness of such interventions are limited. The aim of the study was to describe trends of DKA at onset of childhood T1D during 2005–2014 and assess the impact of a diabetes awareness campaign launched late 2010. Methods: Data of children <12 years presented with DKA at diagnosis were analyzed according to age, gender and year of diagnosis. The frequency and severity of DKA before and during the 4 years campaign were compared. Results: During 2005–2014, 44.9% (243/541) of children diagnosed with T1D presented with DKA. Of these, 22.7% had pH <7.1. In both genders DKA was higher in children <6 years (47.8% vs. 40%; p<0.01) and more severe in <3 years old compared to older children (30% vs. 20%; p<0.01). Following the awareness campaign DKA rate dropped from 48% in 2010 to 39% in 2014 and 15.8% had severe DKA compared to 26.1% in 2005–2010 (p<0.01). This trend was observed in both genders and across age groups. In children <3 years the reduction in DKA frequency and severity was not statistically significant (p=0.15 and p=0.42, respectively). Conclusions: In NWSA, the frequency and severity of DKA at onset of childhood T1D were reduced following 4 years awareness campaign; but the rate is still high. Maintaining the campaign may result in further improvement following a longer period of observation.

Background: Assessing the degree of involvement of caregivers for children with type 1 diabetes mellitus (T1DM) in their diabetes care, differences in the degree of involvement based on the method of insulin administration (multiple daily injections: MDI/continuous subcutaneous insulin infusion: CSII), and its effect on glycemic control. Methods : This was a cross-sectional study with T1DM patients, ages 6–13 years using a six question survey derived from the Diabetes Family Responsibility Questionnaire (DFRQ). All caregivers (n=140) and participants between ages 11 and 13 (n=60) completed the survey. Results: Significant differences between MDI and CSII caregiver responses were found for responsibility for giving insulin boluses, as well as for rotation of infusion/injection sites (p<0.001 and p=0.03, respectively). A sub-analysis of caregiver responses for caregiver versus child responsibility for giving infusion boluses (excluding shared responsibility) showed that 36% of children in the CSII group had primary responsibility for giving insulin boluses, compared to 17% in the MDI group (p<0.001). The median agreement for all questions combined between participants and caregivers for ages 11–13 (n=60 pairs) was “poor” (κ=0.18). No significant effect of parental involvement on last 2-year average HbA 1C was found for CSII or MDI groups (p>0.20). Conclusions: Caregiver reported diabetes care responsibility (mostly parent, mostly child, shared between parent and child) varies for certain aspects of diabetes related care for children ages 6–13, depending upon the mode of insulin administration. Based on the reported degree of parental collaboration, HbA 1C did not differ significantly. However, long-term effects are yet to be determined in longitudinal studies.

Background: The aim of this study was to compare resistivity index (RI) in type 1 diabetic patients and normal controls and to evaluate whether high RI is associated with different biomarkers of diabetic nephropathy (DN) as early detection of DN offers the best chance of delaying or possibly preventing progression to end-stage renal disease. Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of glycosylated hemoglobin, lipid profile and urine samples were taken for assessment of albumin/creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP) and kidney injury molecule-1 (Kim-1). Forty-five diabetic patients and 30 controls had a renal Doppler ultrasonography. t-Test or Mann Whitney U-test for independent variables, Pearson’s or Spearman correlation analysis were used. Results: The mean age of diabetic patients was 16.3±1.5 years, and mean duration of diabetes was 9.4±2.9 years. RI, albumin/creatinine ratio, NGAL, Kim-1 and L-FABP were significantly higher in diabetics than in controls. RI, NGAL, Kim-1, and L-FABP were significantly higher in microalbuminuric compared to normoalbuminuric diabetics. In normoalbuminuric diabetics, RI, NGAL, Kim-1 and L-FABP were significantly higher compared to controls. The study revealed significant positive correlation between the RI in diabetics and both KIM-1 and albumin/creatinine ratio. Conclusions: Increased RI and renal biomarkers in diabetics are early sensitive specific markers of DN, even preceded the development of microalbuminuria, denoting that they can be used as an early and sensitive markers for early detection of DN.

Background: During conservative treatment, congenital hyperinsulinism (CHI) can resolve spontaneously. This study describes the hormonal and metabolic profiles in three patients with ABCC8/KCNJ11 mutations in clinical remission. Methods: An age-adapted fasting and oral glucose tolerance test (OGTT) were performed. Results: All patients (aged 6–9 years) tolerated age-adapted fasting durations (20, respectively 24 h), without reaching glucose concentrations ≤2.5 mmol/L, nor developing hypoglycemia-related symptoms. Nevertheless, insulin concentrations from all patients exceeded the 90th reference percentile at the end of the fasting test (range: 4.2–15.8 mU/L). During the OGTT, one patient (patient 2; BMI: 23.4 kg/m 2 ; age: 7 years) reached a glucose concentration of 11.4 mmol/L after 2 h (concomitant insulin concentration: 148.3 mU/L). Conclusions: The insulin concentration profiles in CHI patients in apparent clinical remission range from almost complete normalization to persistent, yet attenuated, hypersecretion. The hyperglycemia, detected during the OGTT, must be further monitored.

Background: The prevalence of obesity in children and adolescents has increased significantly worldwide with an alarming rise of its co-morbidities. The excess of visceral adipose tissue is associated with hypertension, prothrombotic and pro-inflammatory states. Our aim was to find a possible association between visceral obesity and plasma fibrinogen, as one of the cardiovascular risk factors, in obese children. Methods: Forty-three obese children and 40 non-obese controls were studied regarding their history, complete physical examination, anthropometric assessment, body composition analysis, ultrasonographic measurement of visceral adipose tissue and subcutaneous fat as well as laboratory measurement of plasma fibrinogen. Results: Our study revealed significant higher levels of fibrinogen in obese children than controls (14.5+5.1 and 2.9+0.52 mg/mL, respectively) with p-value <0.01. Moreover, the obese group had statistically significant difference in visceral fat (5.96+0.77 cm) and subcutaneous fat (2.66+0.70 cm) than controls (2.45+0.65 and 0.70+0.18 mg/mL, respectively) with p-value <0.01. In addition, fibrinogen had significant positive correlation with body mass index (r=0.327), waist/hip ratio (r=0.394), fat percentage (r=0.301), visceral adipose tissue (r=0.323) and subcutaneous fat (r=0.301). Conclusions: There was highly significant increase in the fibrinogen level, visceral and subcutaneous abdominal fat in the obese group with insignificant sex differences. Fibrinogen had a significant positive correlation with the different adiposity markers, blood pressure, visceral and subcutaneous fat. Visceral adipose tissue is a stronger predictor for cardiovascular risk compared to subcutaneous fat.

Background: Pituitary hyperplasia secondary to primary longstanding hypothyroidism has been reported in the literature in adults and rarely in children. Methods: Here we present the clinical presentation and diagnostic procedures in eight children with pituitary hyperplasia due to autoimmune thyroiditis, highlighting common findings, such as growth delay, fatigue or gaining weight, but also exceptional findings such as pericardial effusion, rhabdomyolysis, isolated hypertrichosis, and Van Wyk-Grumbach syndrome, which have rarely or never been described. Results and conclusions: Surprisingly no thyroid enlargement was detected. We discuss the unusual presenting signs of autoimmune thyroiditis that should raise the suspicion of pituitary hyperplasia. We suggest that a more elaborate clinical assessment and even modification of the diagnostic approach to autoimmune thyroiditis is needed in order to avoid its serious complications.

Background: The growth hormone (GH) stimulation protocols for clonidine and arginine tests are non-standardized and can be lengthy. We examined the specificity of both tests using a shorter duration of timed samples: 90 min for clonidine and 60 min for arginine. Methods: We retrospectively studied all children who had GH stimulation with clonidine and arginine to test for GH deficiency (GHD). We compared the diagnostic accuracy of both reference and new shortened test (index). Results: We reviewed 243 charts (11.4±4.1 years old; 74.5% males). The combined reference test was performed on 159 children, 29 (18.3%) tested positive for GHD on the combined index test, Kappa 0.98, false positive rate 1 (0.8%), specificity 0.99, 95th CI (0.96–1), and p=1.0. The specificity of both the clonidine and arginine single index tests was 0.98%. Conclusions: The shortened clonidine and arginine stimulation index tests have good specificity. This is a viable option for testing children for GHD.

Background: The aim of the study was to define the prevalence and degree of advanced bone age (ABA) in normal vs. excessive weight children, and identify variables affecting ABA. Methods: We studied 167 children (3–18 years) with normal weight (28 F, 28 M), overweight (8 F, 12 M), and obesity (OB) (63 F, 28 M) at AI duPont Hospital for Children. We assessed bone age (BA), insulin, leptin, estradiol (E2), DHEAS, and IGF-1 levels. Results: Almost 25% of OB children have ABA>2 SDS, 33% >2 years (range 2–6.5 years advanced). ABA correlated with leptin, DHEAS and BMI z-score in girls, and with IGF-1 z-score and BMI z-score in boys (p<0.01). Girls with ABA had higher BMI z-score (p<0.001), insulin levels (p=0.02), and rates of weight gain (p=0.03). Boys with ABA had greater BMI z-score (p<0.001), but rate of weight gain did not differ. The greatest degree of ABA was found combining variables by tertiles. The top tertile of BA/CA had the highest insulin and IGF-1 z-scores. The top combined tertiles of DHEAS and BMI z-score or DHEAS and leptin in girls had the highest BA/CA. In boys, the top tertiles of BMI z-score and IGF-1 z-score produced the highest BA/CA. The lowest combined tertiles of any variables related to the lowest BA/CA. Conclusions: Multiple factors influence skeletal maturation. Almost 25% of children with OB have ABA, associated with BMI z-score, and one or more of the following: insulin, leptin, DHEAS, IGF-1, and rate of weight gain. This report delineates the prevalence and degree of ABA by sex, in children with normal versus excessive weight.

Background: The majority of pediatric patients with Graves’ disease will ultimately require definitive therapy in the form of radioactive iodine (RAI) ablation or thyroidectomy. There are few studies that directly compare the efficacy and complication rates between RAI and thyroidectomy. We compared the relapse rate as well as the acute and long-term complications of RAI and total thyroidectomy among children and adolescents with Graves’ disease treated at our center. Methods: Medical records from 81 children and adolescents with a diagnosis of Graves’ disease who received definitive therapy over a 12-year period were reviewed. Results: Fifty one patients received RAI and 30 patients underwent thyroidectomy. The relapse rate was not significantly different between RAI and thyroidectomy (12.1% vs. 0.0%, p=0.28). There were no acute or long-term complications in the RAI group, but there were eight cases of hypoparathyroidism (two transient and six permanent) in the thyroidectomy group. None of the patients developed a recurrent laryngeal nerve injury. Conclusions: RAI is a safe and effective option for treatment of children and adolescents with Graves’ disease. In light of the rate of permanent hypoparathyroidism seen at our center with thyroidectomy and previously published long-term safety of RAI, we recommend RAI as the first line treatment for children and adolescents with Graves’ disease. For those centers performing thyroidectomies, we recommend that each center select 1–2 high-volume pediatric surgeons to perform all thyroid procedures, allowing individuals to increases case volume and potentially decrease long-term complications of thyroidectomy.

Background: Hereditary tyrosinemia type 1 (HT1) is a rare inborn error of tyrosine catabolism with a worldwide prevalence of one out of 100,000 live births. HT1 is clinically characterized by hepatic and renal dysfunction resulting from the deficiency of fumarylacetoacetate hydrolase (FAH) enzyme, caused by recessive mutations in the FAH gene. We present here the first report on identification of FAH mutations in HT1 patients from Pakistan with a novel one. Methods: Three Pakistani families, each having one child affected with HT1, were enrolled over a period of 1.5 years. Two of the affected children had died as they were presented late with acute form. All regions of the FAH gene spanning exons and splicing sites were amplified by polymerase chain reaction (PCR) and mutation analysis was carried out by direct sequencing. Results of sequencing were confirmed by restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Three different FAH mutations, one in each family, were found to co-segregate with the disease phenotype. Two of these FAH mutations have been known (c.192G>T and c.1062+5G>A [IVS12+5G>A]), while c.67T>C (p.Ser23Pro) was a novel mutation. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals. Conclusions: Most of the HT1 patients die before they present to hospitals in Pakistan, as is indicated by enrollment of only three families in 1.5 years. Most of those with late clinical presentation do not survive due to delayed diagnosis followed by untimely treatment. This tragic condition advocates the establishment of expanded newborn screening program for HT1 within Pakistan.

Background: McCune-Albright syndrome (MAS) is characterized by the triad of polyostotic bone fibrous dysplasia (PFD), endocrine disorders, and café-au-lait skin pigmentation. Ninety percent of MAS patients have fibrous dysplasia (FD) craniofacial lesions. Osteonecrosis of the jaw (ONJ) has been described as an adverse side effect of bisphosphonate therapy. The aim of the study was to investigate evidence of clinical and/or radiological signs of ONJ in FD/MAS pediatric patients due to bisphosphonate therapy and describe odontoiatric tools in this population. Methods: Thirteen FD/MAS patients were enrolled. All patients during pediatric age have been treated with pamidronate infusions. They underwent complete oral clinical examination. Ortopantomography and/or CT were evaluated in all cases. Results and conclusions: No patient developed ONJ. None of them showed radiological signs different from jaw FD. In spite of the low number of patients enrolled, results confirm that, in this population, ONJ can be ruled out as a chronic adverse side effect of bisphosphonate therapy.

Background: Bisphenol A (BPA) is known as an endocrine disruptor and it is supposed to have a role on the development of central precocious puberty (CPP). Kisspeptin, a hypothalamic peptide, is a neuromodulator of gonadotropin releasing hormone and it has an important role on regulation of the onset of puberty. The BPA levels in girls with CPP and premature thelarche (PT) and its relation with kisspeptin levels were investigated. Methods: Twenty-eight girls with CPP, 28 girls with PT and 22 prepubertal girls as a control group were enrolled to the study. Urinary BPA and serum kisspeptin levels were compared in the groups. Bivariate correlations were performed to evaluate the relations of BPA with kisspeptin and estradiol. Results: There was no statistical difference between groups regarding BPA levels. Serum kisspeptin levels were higher in CPP group than controls [306.56 (interquartile range (IQR), 175.63–504.66) vs. 157.62 (IQR, 55.61–285.00) p: 0.008]. There were no correlations between BPA and kisspeptin levels (r: 0.088, p: 0.391) and between BPA and estradiol (r: –0.171, p: 0.144). Conclusions: The BPA levels did not differentiate between groups and it seems that the exposed amount of BPA in daily life did not affect kisspeptin levels in girls with CPP and PT.

Background: Menstruation in the teenage age has assumed variable trends which is been influenced by several variables. This study is aimed at determining the pattern and trend of menstruation among teens attending secondary school in south east Nigeria and associated factors. Methods: Menstruation patterns were investigated using a stratified random sampling method of teens from junior secondary schools in Enugu, south east Nigeria. A self-administered questionnaire was developed and data analyzed using SPSS version 19. Results: A total of 897 female teenagers aged 9–18 years completed the questionnaire with a mean age of 13.9±1.9 years. The mean age (SD) at onset of menarche was 12.5±1.2 years. Teenage girls with higher BMI achieved menarche earlier at age 8 and 9 when compared with their counterparts with lower BMI and this is statistically significant. F=7.60, df=8, p<0.001. Teens with a 14-day cycle had a higher BMI when compared with teens with longer cycle but this is not statistically significant. F=1.05, df=4, p=0.381. There is a statistical significance difference between teens duration of menstrual flow and BMI. Those with higher BMI had longer duration(4–5 days) compared with those with lower BMI. F=3.329, df=4, p=0.01 Conclusions: This study revealed that the mean age at onset of menarche was 12.5±1.2 years showing a continuing decreasing trend. Teens with higher BMI attain menarche earlier and had longer days of periods when compared with their counterpart with lower BMI.

Background: Current clinical practice is to evaluate children presenting with premature adrenarche (PA) for non-classical congenital adrenal hyperplasia (NC-CAH). Our main objective was to assess the prevalence of NC-CAH among children presented with PA. Additional objectives were to ascertain whether subpopulations were prone to NC-CAH, and therefore justified to be tested, and if obesity is a factor that can exclude the need for CAH testing. Methods: A retrospective chart review of all children ≤11 years, who presented to our clinic with PA between January 2012 and May 2015 (n=103) was conducted. PA was defined based on commonly accepted clinical criteria. Results: We did not identify any subjects with NC-CAH but one was affected with previously undiagnosed classical simple virilizing CAH (SV-CAH). The subject was born prior to the implementation of CAH newborn screening in the state of birth. The affected subject was of Middle Eastern origin and also obese (BMI >95 percentile for age and sex). Conclusions: Undiagnosed CAH is an uncommon cause of PA, and therefore routine screening for NC-CAH in every case of PA may not be justified, although, perhaps, should still be considered in high risk ethnicities. Obesity does not appear to exclude the possibility of being affected with mild or NC-CAH.

Background: Obesity is a global health problem affecting all age groups. Childhood obesity, which may cause chronic diseases including diabetes mellitus, cardiovascular disease and cancer, etc., deserves more attention. However, few studies highlight the association between childhood obesity and psychological diseases. In the present study, we aimed to evaluate the psychological condition in obese children. Methods: One hundred and sixty-seven obese (body mass index (BMI) >95th percentile) and 200 normal weight children (BMI between 5th and 85th percentile) aged 9–16 years were enrolled into this case-control study. In order to assess the self-concept, anxiety and depression levels: the Piers-Harris Children’s Self-Concept Scale (PHCSCS), state and trait anxiety inventory for children (STAI-C) and the children depression inventory (CDI) were administered both obese and control groups. Results: There were significant differences among obese and control groups in terms of the total score of PHCSCS [55 (22–69) versus 65 (57–74)], STAI-C [37 (20–55) versus 28 (20–42)], and CDI [12 (4–39)] versus [8 (3–19)]; respectively (p<0.001, p<0.001, p<0.001). We also found statistically significant differences among groups in all of the subscales parameters of PHCSCS (p<0.001). Conclusions: Our results indicate that obese children may experience psychiatric disorders more than normal-weight peers.

Here, we describe three cases of loss-of-function mutations in the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) domain of dual oxidase 2 ( DUOX2 ) occurring along with concurrent missense mutations in thyroid peroxidase ( TPO ), leading to transient congenital hypothyroidism (CH). Three Japanese boys with nonconsanguineous parents were diagnosed with CH during their neonatal screenings. All patients presented with moderate-to-severe neonatal hypothyroidism and were diagnosed with transient CH after re-evaluation of thyroid function. Two siblings were compound heterozygous for p.[R1110Q]+[Y1180X] in DUOX2 ; one of them was also heterozygous for p.[R361L] in TPO . The third patient was compound heterozygous for p.[L1160del]+[R1334W] in DUOX2 and heterozygous for p.[P883S] in TPO . This is the first report of a de novo L1160del mutation affecting the DUOX2 gene and of the novel mutations Y1180X in DUOX2 and R361L in TPO . R1110Q and L1160del were found to reduce H 2 O 2 production (5%–9%, p<0.01), while Y1180X, which introduces a premature stop codon, did not confer detectable H 2 O 2 production (–0.7%±0.6%, p<0.01). Moreover, R1334W, a missense mutation possibly affecting electron transfer, led to reduced H 2 O 2 production (24%±0.9%, p<0.01) in vitro, and R1110Q and R1334W resulted in reduced protein expression. Y1180X was detected in a 120 kDa truncated form, whereas L1160del expression was maintained. Further, R361L, a novel missense mutation in TPO , caused partial reduction in peroxidase activity (20.6%±0.8%, p=0.01), whereas P883S, a missense variant, increased it (133.7%±2.8%, p=0.02). The protein expression levels in the case of R361L and P883S were maintained. In conclusion, we provide clinical and in vitro demonstrations of different functional defects and phenotypic heterogeneity in the same thyroid hormonogenesis pathway.

Background: Hyperglycemic ketoacidosis is an acute, life threatening condition requiring early etiologic recognition and management to prevent serious morbidity/mortality. The most common cause is diabetic ketoacidosis (DKA). Organic acidemias (OAs) are inheritable disorders caused by defects in protein metabolism resulting in acid accumulation. Patients with metabolic decompensation usually present with acidosis, with/without hypoglycemia. Hyperglycemia is a very rare manifestation. At least 16 cases of OAs presenting with hyperglycemia have been reported. Six of the 16 were diagnosed with isolated methylmalonic academia (MMA) and three of the six passed away from late diagnosis. Case description: We describe a 2-year-old Thai girl who presented with hyperglycemia, acidosis and ketosis. She has underlying delayed development, seizures, optic atrophy and poor growth. An initial diagnosis of DKA was made and standard treatment was started. After 4 h of treatment, the patient partially responded to treatment; blood sugar decreased but acidosis and ketonemia persisted. HbA 1c was normal. Investigations to rule out OAs were performed. Markedly elevated urinary methylmalonic acid consistent with MMA was observed. Molecular and enzyme analyses confirmed the diagnosis with isolated MMA. Specific treatment for MMA including protein restriction, high caloric fluid, carnitine and vitamin B12 was promptly started. Clinical improvement was seen 4 days after initiating specific treatment. Conclusions: Inherited metabolic disorders should be included in differential diagnosis in hyperglycemia ketoacidosis patients who respond poorly to standard DKA treatment. Unusual findings, e.g. hyperammonemia, lactic acidosis, pancytopenia, abnormal basal ganglia in MRI or underlying delayed development may indicate underlying OAs. Determining the etiology of hyperglycemic ketoacidosis is important and can lead to good outcomes.

Background: The aim of the study was to investigate the incidence and genotype-phenotype characteristics of UDP-galactose-4′-epimerase (GALE) deficiency in newborn screening of Chinese population. Methods: Neonates were screened at the Newborn Screening Center of Zhejiang Province, China for GALE deficiency and their condition was confirmed by testing of the GALE gene and GALE enzyme. Clinical and laboratory follow-up data were recorded. Results: A total of 350,023 of newborns were screened; of which, the condition of one female neonate was diagnosed with GALE deficiency, accounting for an incidence rate of approximately 1:350,000 in our sample. The patient with GALE deficiency clinically manifested slight increase in levels of blood galactose (122–251 mg/L), glutamyl endopeptidase (61 U/L), total bile acid (17 μmol/L), and lactic acid (1.8 mmol/L). The neonate was fed with lactose-free powdered milk and followed-up to 1 year. Re-examination showed that all biochemical indicators recovered to normal range, whereas physical and mental development appeared normal without cataract change. The genotype of GALE deficiency was identified as compound heterozygous mutations: c.505C>T (p.R169W) and c.452G>A (p.G151D). The latter was a novel mutation. The GALE enzyme value was 42% of control. Conclusions: GALE deficiency is relatively rare in China. The genotype of compound heterozygous mutations at R169W and G151D clinically manifest as mild-type; it is recommended to limit galactose diet.

Hyperinsulinism-hyperammonemia (HI/HA) syndrome, often characterized by recurrent symptomatic hypoglycemia and persistent hyperammonemia, is the second most frequent cause of the congenital hyperinsulinism (CHI). Here, we reported a patient with normal birth weight, repeated seizures, untreatable hypoglycemia, and persistent, mild hyperammonemia. The genetic diagnosis revealed that the patient carried a heterozygous, de novo missense mutation (N410I, c.1401A>T) in the glutamate dehydrogenase 1 gene ( GLUD1 ). The patient was treated with diazoxide, which significantly alleviated the hypoglycemia. CT and MRI brain scanning at different developmental stages revealed large-scale brain damage in the front lobe. Severe neurodevelopment deficits were identified in the follow-up.