Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise molecular diagnosis is essential because it leads to optimal treatment of the patients and allows early diagnosis for their asymptomatic family members. Mutations in the glucokinase ( GCK) (MODY 2) and hepatocyte nuclear factor ( HNF)1A/4A (MODY 3 and MODY 1) genes are the most common causes of MODY. GCK mutations cause a mild, asymptomatic, and stable fasting hyperglycemia usually requiring no specific treatment. However, mutations in the HNF1A and HNF4A cause a progressive pancreatic β-cell dysfunction and hyperglycemia that can result in microvascular complications. Sulfonylureas are effective in these patients by acting on adenosine triphosphate (ATP)-sensitive potassium channels, although insulin therapy may be required later in life. Mutations in the HNF1B (MODY 5) is associated with pancreatic agenesis, renal abnormalities, genital tract malformations, and liver dysfunction. Compared to MODY 1, 2, 3, and 5, the remaining subtypes of MODY have a much lower prevalence. In this review, we summarize the main clinical and laboratory characteristics of the common and rarer causes of MODY.

September 11, 2014

Relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy in adolescent type 1 diabetic patients

Soha M. Abd El Dayem, Ahmed A. Battah, Abo El Magd El Bohy, Amal El Shehaby, Esmat Abd El Ghaffar

Page range: 265-273

Abstract

Objective: Our objective was to evaluate the relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy (CAN) in adolescent type 1 diabetic patients. Patients and 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 chemerin, vaspin, asymmetric dimenthylarginine (ADMA), and oxidized low-density lipoprotein (OxLDL) by enzyme-linked immunosorbent assay (ELISA) technique. Also, blood samples were taken for analysis of glycosylated hemoglobin; lipid profiles and urine samples were taken for assessment of albumin/creatinine ratio. Twenty-four-hour holter [for assessment of time domain heart rate variability (HRV)] and carotid intima-media thickness (CIMT) were also done. The t-test or Mann-Whitney U-test for independent variables, Pearson’s or Spearman’s correlation, and stepwise multiple regression 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. Chemerin, vaspin, OxLDL, and albumin/creatinine ratio were significantly higher, whereas ADMA was significantly lower than the controls. By stepwise multiple regression analysis, vaspin had a relation with a standard deviation difference RR (SDARR) and waist/height ratio. Conversely, chemerin had a relation with OxLDL. Albumin/creatinine ratio had a significant positive correlation with chemerin and OxLDL, and a negative correlation with ADMA. Conclusions: Type 1 diabetic patients had impaired time domain HRV associated with increased CIMT. Vaspin had a significant relation to CAN, whereas chemerin, ADMA, and OxLDL had a significant correlation with albumin/creatinine ratio that reflects their role in renal affection.

September 11, 2014

How does autoimmune thyroiditis in children with type 1 diabetes mellitus influence glycemic control, lipid profile and thyroid volume?

Katarzyna Korzeniowska, Anna Ramotowska, Agnieszka Szypowska, Agnieszka Szadkowska, Wojciech Fendler, Barbara Kalina-Faska, Wojciech Młynarski, Przemyslawa Jarosz-Chobot, Malgorzata Myśliwiec

Page range: 275-278

Abstract

Aim: To investigate whether autoimmune thyroiditis (AIT) in children with type 1 diabetes mellitus (DM1) has any influence on glycemic control, lipid profile or thyroid volume. Methods: A total of 330 patients with DM1 and AIT (DM1+AIT group) were compared with 309 children with DM1 without AIT (control group). Patients were treated in four Polish academic pediatric diabetes centers from 2008 to 2012: Warsaw, Lodz, Katowice and Gdansk. All patients underwent measurements of thyroid-stimulating hormone (TSH), free thyroxine, anti-thyroid peroxidase (anti-TPO) antibody, anti-thyroglobulin (anti-TG) antibody and HbA 1c levels, and thyroid ultrasound examination. Results: Among AIT+DM1 patients, 62% (n=205) were female, whereas in the control group 60.8% (n=188) were male (p < 0.0001). Children with AIT+DM1 had lower a BMI-SDS (mean difference of –0.5, 95% CI –0.68 to –0.33; p < 0.0001), had a higher SDS thyroid volume (0.27, 95% CI 0.03–0.51; p=0.014) and needed less insulin (–0.15, 95% CI –0.20 to –0.11 U/kg body weight per day; p < 0.0001) in comparison with the control group. AIT patients had higher HbA 1c levels (0.66, 95% CI 0.36%–0.96%, p < 0.0001), lower HDL-cholesterol levels (–3.68, 95% CI –1.41 to –5.94 mg/dL, p=0.002) and higher triglyceride levels (7.16, 95% CI 1.22–13.10 mg/dL, p=0.02). Patients with positive anti-TPO and anti-TG antibodies were older (by 1.95 years, 95% CI 0.98–2.92 years, p=0.006) and had longer DM1 duration (by 1.64 years, 95% CI 0.76–2.52 years, p=0.006). Presence of anti-TPO antibodies was associated with higher TSH levels (odds ratio 2.34, 95% CI 1.36–4.04; p=0.007). Conclusion: AIT accompanying DM1 is associated with worse glycemic control and lipid profile as well as a lower daily insulin requirement. The female gender is more likely to develop AIT and hypothyroidism.

September 27, 2014

Profile of mood states in adult type 1 diabetes mellitus men and women with disease onset in childhood and in adulthood

Lina Lašaitė, Rytas Ostrauskas, Rimantas Žalinkevičius, Nijolė Jurgevičienė, Lina Radzevičienė

Page range: 279-285

Abstract

Introduction: Although diabetes may not be associated with psychopathology, it may be associated with less severe disturbances in psychosocial functioning. Emotional problems in relation to type 1 diabetes are usually analysed as symptoms of psychiatric conditions but not as states of mood. The aim was to compare profiles of mood states in adult patients with childhood-onset and adulthood-onset type 1 diabetes mellitus and to outline possible gender-specific differences. Subjects and methods: A total of 214 adult type 1 diabetic patients were randomly selected from the Lithuanian Diabetes Registry. The mood states were compared in 105 (42 men and 63 women) patients with type 1 diabetes diagnosed during 0–18 years of life and in 109 (61 men and 48 women) diagnosed in adulthood. The scores of tension-anxiety, depression-dejection, anger-hostility, vigour-activity, fatigue-inertia and confusion-bewilderment were evaluated using the Profile of Mood States. Results: Depression-dejection was higher in adulthood-onset diabetic women than in childhood-onset (p=0.005) diabetic patients. In childhood-onset diabetic patients depression-dejection (p=0.046) and confusion-bewilderment (p=0.033) were higher in women than in men. Adulthood-onset women with diabetes had higher tension-anxiety (p=0.027), depression-dejection (p=0.001), and confusion-bewilderment (p=0.004) scores than men. Multiple logistic analyses showed that adulthood-onset period of type 1 diabetes is associated with higher levels of depression-dejection [OR=1.1; 95% confidence intervals (CI) 1.01–1.19, p=0.025], longer diabetes duration (OR=2.00; 95% CI 1.27–2.03, p=0.012), higher HbA1c level (OR=1.15; 95% CI 1.02–1.3, p=0.023), and female gender (OR=2.51; 95% CI 1.29–2.90, p=0.021). Conclusions: Profile of mood states in adult women with type 1 diabetes is worse than in men. Adulthood-onset type 1 diabetic women have higher depression-dejection than do childhood-onset diabetic patients. Adulthood-onset period of type 1 diabetes is associated with higher levels of depression-dejection, longer diabetes duration and female gender.

January 14, 2015

Evaluation of fetuin-A and carotid intima-media thickness in adolescent type 1 diabetic patients

Soha M. Abd El Dayem, Ahmed A. Battah, Abo El Magd El Bohy, Amal El Shehaby

Page range: 287-292

Abstract

Objective: To evaluate fetuin-A level and carotid intima-media thickness (CIMT) in adolescent type 1 diabetics. Patients and methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin (HbA1), lipid profile, and fetuin-A. Urine sample was also taken for assessment of albumin/creatinine ratio. Anthropometric measurements were taken, including weight, height, and waist and hip circumference. CIMT was assessed for all patients and controls. Results: Serum fetuin-A, Rt., Lt. and both CIMT were significantly higher in diabetics. Fetuin-A had a significant positive correlation with duration of disease, waist and hip circumference, BMI, BMI SDS, waist/height ratio, Rt., Lt. and both CIMT. Stepwise multiple regression analysis revealed that the duration of disease, waist/height ratio, and HDL-c were the factors related to fetuin-A. Conclusion: Adolescent type 1 diabetic patients have high fetuin-A levels and increased CIMT, with the latter representing the development of early atherosclerosis. In this light, adolescents with type 1 diabetes require frequent follow up for early detection of atherosclerosis.

January 10, 2015

An increasing incidence of type 1 diabetes mellitus in Romanian children aged 0 to 17 years

Viorel Serban, Stuart Brink, Bogdan Timar, Alexandra Sima, Mihaela Vlad, Romulus Timar, Adrian Vlad

Page range: 293-298

Abstract

Background: The epidemiology of type 1 diabetes mellitus may provide insights into the pathogenesis of the disease. Objective: The aim of this work was to characterize the trend of the incidence of type 1 diabetes mellitus in Romanian children aged from 0 to 17 years over a 10-year interval. Subjects and methods: Data regarding new cases were obtained from two sources: (1) The Romanian Childhood Diabetes Registry and (2) Records of the Medical Center “Cristian Serban”, Buzias. The demographic data were retrieved from the National Institute for Statistics. The incidence was calculated for the age groups 0–4, 5–9, 10–14, and 15–17 years. Results: A total of 3196 new cases, aged below 18 years, were found by both the sources. There were significant differences between the groups (p=0.012), the mean incidence being highest in the age group 10–14 years (9.6/100,000/year, 95% CI 9–10.1) and lowest in children aged from 0 to 4 years (4.8/100,000/year, 95% CI 4.4–5.3). Boys were slightly more frequently affected than girls (p=0.038). The age and gender adjusted incidence of type 1 diabetes mellitus increased significantly (p<0.001) from 6.2/100,000/year (95% CI 5.5–6.9) in 2002 to 9.3/100,000/year (95% CI 8.4–10.3) in 2011. The raise in incidence was noticed in all age groups except for 15–17 years. Conclusion: Romania is a country with an intermediate incidence of type 1 diabetes mellitus in children, which is slightly higher in boys than in girls. The incidence of type 1 diabetes mellitus increased continuously during the 10-year survey, with the exception of the oldest teens.

February 18, 2015

Resistin and right ventricular function in children with recently diagnosed type-1 diabetes mellitus: a case control study

Mohammed A. Al-Biltagi, Osama A. Tolba, Wegdan Mawlana, Abdallah Abd El Hamed, May Ghazy

Page range: 299-308

Abstract

Background: Resistin is an adipocyte-derived signaling polypeptide described in adipose tissue, which acts as a metabolic link between inflammation and atherosclerosis. This study aimed to assess the relation between right ventricular (RV) function assessed by echocardiography and resistin levels in recently diagnosed type-1 diabetic children. Methods: The study was conducted as a prospective cohort study and it included 30 children with type-1 diabetes mellitus as a patient group and 30 healthy children matched for age and sex as controls. It evaluated RV functions by tissue Doppler imaging, speckle tracking imaging, and real-time three-dimensional echocardiography (RT3DE), as well as assessing resistin serum level using enzyme-linked immunosorbent assay. Results: The left ventricle (LV) showed no significant difference between the two groups in E/A ratio across the mitral valve, ejection fraction, and S wave mitral annulus. However, it showed significant decrease in the E′/A′ wave of mitral annulus, impairment of LV myocardial performance index (MPI), and decrease in LV EF measured by RT3DE in diabetic patients compared to the control group. Significant differences in the mean value of tricuspid annular systolic excursion (TASE), pulmonary artery pressure, longitudinal systolic strain (RV LSS), MPI, and RV ejection fraction were observed between the studied groups. Yet, no significant differences in E/A ratio and S value were observed between the two groups. Significant positive correlation of resistin level with age of studied group and significant negative correlation of resistin with both TASE and RV LSS values were also observed. Conclusion: We confirmed the presence of subclinical RV systolic and diastolic dysfunction in type-1 diabetic children with positive correlation between resistin level and RV dysfunction among them.

February 21, 2015

Assessment of human cartilage glycoprotein 39 (YKL-40), preptin, and nitric oxide in adolescent patients with type 1 diabetes and its relation to cardiorenal affection

Soha M. Abd El Dayem, Ahmed A. Battah, Amal El Shehaby, Nagwa Abd Allah

Page range: 309-314

Abstract

Aim: To evaluate new biomarkers such as YKL-40, preptin, and nitric oxide (NO) in patients with diabetes and to assess its relation to cardiorenal injury. Patients and methods: The study included 62 patients with type 1 diabetes and 30 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile, YKL-40, preptin, and NO. Also, urine sample was taken for analysis of albumin/creatinine ratio. Echocardiography was also done. Results: NO was lower, whereas YKL-40, preptin, and albumin/creatinine ratio were significantly higher in patients with diabetes. NO had a significant negative correlation with LVEDD, LVESD, PWT, LV mass, YKL-40, preptin, and albumin/creatinine ratio. YKL-40 had a significant positive correlation with waist/height ratio, preptin and negative correlation with E/A ratio. Stepwise multiple regression revealed that E/A ratio is the only parameter related to YKL-40. On the contrary, NO and systolic blood pressure are related to preptin. Conclusion: A significant reduction of NO and elevation of YKL-40 and preptin was found in patients with diabetes. A decrease in NO is associated with diastolic dysfunction, LV hypertrophy, and renal impairment, whereas YKL-40 is associated with diastolic dysfunction. An increase in preptin level was associated with hypertension.

March 7, 2015

The effect of a home-based strength training program on type 2 diabetes risk in obese Latino boys

Louise A. Kelly, Armando Loza, Xiao Lin, E. Todd Schroeder, Adrienne Hughes, Alison Kirk, Ann-Maire Knowles

Page range: 315-322

Abstract

Objective: To determine the effects of a home-based strength training (HBST) intervention on insulin sensitivity (SI), compensatory acute insulin response and β-cell function, body composition measures, and maximum strength in obese Latino boys. Methods: A total of 26 obese Latino males aged between 14 and 18 years were randomized to either a twice-weekly (n=15) or a control group (C; n=15) for 16 weeks. HBST for 16 weeks, composed of two 1-h sessions per week. Outcome measures were assessed pre-and post-intervention/control condition and included SI, acute insulin response to glucose (AIR) and disposition index (DI), fasting glucose, 2-h glucose, body composition using waist-hip circumferences, body mass index (BMI), dual energy X-ray absorptiometry (DEXA) scan, blood pressure, and strength by 1-repetition maximum. A repeated measures GLM was used to assess differences in changes in outcome measures, between the C and the HBST groups. Results: There were no significant overall intervention effects on any of the outcome variables (p<0.05). Conclusion: These results suggest that an HBST does not improve SI, maximal strength or decrease adiposity in obese Latino boys.

September 11, 2014

From cerebral salt wasting to diabetes insipidus with adipsia: case report of a child with craniopharyngioma

Veena Raghunathan, Maninder Singh Dhaliwal, Aditya Gupta, Ganesh Jevalikar

Page range: 323-326

Abstract

Craniopharyngioma is associated with a wide and interesting variety of sodium states both by itself and following surgical resection. These are often challenging to diagnose, especially given their dynamic nature during the perioperative course. We present the case of a boy with craniopharyngioma who had hyponatremia due to cerebral salt wasting preoperatively, developed diabetes insipidus (DI) intraoperatively and proceeded to develop hypernatremia with adipsic DI. Conclusion: Cerebral salt wasting is a rare presenting feature of craniopharyngioma. Postoperative DI can be associated with thirst abnormalities including adipsia due to hypothalamic damage; careful monitoring and a high index of suspicion are required for its detection. Adipsic DI is a difficult condition to manage; hence a conservative surgical approach is suggested.

October 18, 2014

Three years of liraglutide treatment offers continuously optimal glycemic control in a pediatric patient with maturity-onset diabetes of the young type 3

Tatsuhiko Urakami, Masako Habu, Misako Okuno, Junichi Suzuki, Shori Takahashi, Tohru Yorifuji

Page range: 327-331

Abstract

Sulfonylureas (SUs) are recommended as the first-line pharmacological treatment in patients with uncontrolled maturity-onset diabetes of the young type 3 (MODY3). In contrast, glucagon-like peptide-1 (GLP-1) receptor agonists have the advantages of a low risk of hypoglycemia and maintained β-cell function. We report a pediatric patient with MODY3 treated with a GLP-1 receptor agonist, liraglutide. A 12-year-old Japanese girl with MODY3 had been treated with insulin for 6 months since the time of diagnosis. After genetic analysis, we switched her treatment from insulin to liraglutide. After switching to liraglutide, the patient maintained optimal glycemic control with hemoglobin A 1c levels of 6.8%–7.5% and had postprandial C-peptide levels >3.0 ng/mL during a 3-year treatment period. No adverse events associated with liraglutide were observed. GLP-1 receptor agonists are the potential medications for patients with MODY3 who maintain residual insulin secretion.

November 25, 2014

Diabetic euglycemic ketoacidosis in newly diagnosed type 1 diabetes mellitus during Ramadan fasting

Veysel Nijat Baş, Salih Uytun, Yasemin Altuner Torun

Page range: 333-335

Abstract

Real euglycemic diabetic ketoacidosis [DKA; blood glucose <200 mg/dL (11.1 mmol/L)] is rare, and long-lasting starvation conditions due to intervening diseases in type 1 diabetes mellitus patients may also cause it. Euglycemic DKA is also reported in insulin-dependent diabetics with depression, alcoholics, glycogen storage diseases, and chronic liver disease apart from pregnant cases. This case report is presented to emphasize the importance of evaluation of acid-base state, urine glucose, and ketone values at the application in all newly diagnosed type 1 diabetic patients with normal glucose levels by defining euglycemic DKA that resulted from long-lasting starvation during Ramadan fasting in a newly diagnosed 14-year-old male patient.

August 22, 2014

Transient neonatal hyperinsulinism with adaptation disorders: a report of three cases

Hiroshi Mizumoto, Hiroko Uchio, Sumie Yamashita, Daisuke Hata

Page range: 337-340

Abstract

Transient hyperinsulinism can occur in neonates following exposure to perinatal stress, such as intrauterine growth restriction and birth asphyxia. However, little is known about its pathophysiology and clinical manifestations. We report three neonatal cases of transient severe hyperinsulinism complicated with cardiopulmonary problems, thrombocytopenia, and marked erythroblastosis at birth. All cases showed signs of placental insufficiency, indicating that chronic hypoxia and malnutrition during fetal development might be associated with characteristic clinical features after birth. Perinatal stress-associated hyperinsulinism can be regarded as a systemic syndrome characterized by cardiopulmonary and hematological problems due to fetal chronic hypoxia.

August 19, 2014

Acute mononeuropathy in a child with newly diagnosed type 1 diabetes mellitus

Maria Adriana Rangel, Carolina Baptista, Fátima Santos, Marta Vila Real, Rosa Arménia Campos, Ana Luísa Leite

Page range: 341-344

Abstract

Introduction : Neuropathy is a frequent complication of diabetes mellitus (DM), increasing with the duration of the disease, poor glycemic control and advanced age. Acute presentation of a neuropathy in the setting of a newly diagnosed type 1 DM is rare and holds a diagnostic challenge. Case report : A 10-year-old girl, presented at the emergency service with complaints of polydipsia, polyuria, asthenia and weight lost over the last 15 days, accompanied by difficulties in flexing the right foot, during the previous week. The patient denied any pain, paresthesias, or altered sensibility. There was no fever documented, or recent infectious intercurrence or trauma. On physical examination, she was conscious, collaborative and space and time-orientated, had a diminished strength in the right foot, namely in the dorsiflexion, conditioning a steppage gait ipsilateral. Hyperalgesia was felt in the dorsum of the right feet to the ankle. DM type 1 was diagnosed based on serum glucose of 629 mg/dL and mild ketoacidosis. Investigation for infectious, immune and nutritional aetiologies for the mononeuropathy was negative. Electrophysiological study was suggestive of a lesion of the peroneal nerve on the popliteal cesspit, but was not conclusive. The patient started physiotherapy during her hospital stay and exhibited a slight improvement in the dorsiflexion of the foot. Four months later she was asymptomatic and with good glycaemic control. Conclusion : Diabetic neuropathy is a heterogeneous group that still lacks adequate comprehension. Its approach is empirical and demands exclusion of other etiologies. A definitive diagnosis is not always possible and sometimes is retrospective.

Open Access January 20, 2015

Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture

Shira Harel, Ana S.A. Cohen, Khalid Hussain, Sarah E. Flanagan, Kamilla Schlade-Bartusiak, Millan Patel, Jaques Courtade, Jenny B.W. Li, Clara Van Karnebeek, Harley Kurata, Sian Ellard, Jean-Pierre Chanoine, William T. Gibson

Page range: 345-351

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Abstract

Background: Inheritance of two pathogenic ABCC8 alleles typically causes severe congenital hyperinsulinism. We describe a girl and her father, both homozygous for the same ABCC8 mutation, who presented with unusual phenotypes. Methods: Single nucleotide polymorphism microarray and Sanger sequencing were performed. Western blot, rubidium efflux, and patch clamp recordings interrogated the expression and activity of the mutant protein. Results: A 16-month-old girl of consanguineous descent manifested hypoglycemia. She had dysregulation of insulin secretion, with postprandial hyperglycemia followed by hypoglycemia. Microarray revealed homozygosity for the regions encompassing KCNJ11 and ABCC8 . Her father had developed diabetes at 28 years of age. Sequencing of ABCC8 identified a homozygous missense mutation, p.R1419H, in both individuals. Functional studies showed absence of working K ATP channels. Conclusion: This is the first description of a homozygous p.R1419H mutation. Our findings highlight that homozygous loss-of-function mutations of ABCC8 do not necessarily translate into early-onset severe hyperinsulinemia.

January 12, 2015

Cognitive functioning, metabolic control, and treatment type in youth with type 1 diabetes

Christine A. Limbers, Kara Emery, Danielle Young, Matthew Stephen

Page range: 353-355

Abstract

Background: There is growing evidence that cognitive functioning plays an important role in self-care behavior and glycemic control in pediatric patients with type 1 diabetes. The aim of this pilot study was to examine whether there were differences in glycemic control and cognitive functioning between youth with T1D treated with continuous subcutaneous insulin infusion and multiple daily injections. Methods: The sample consisted of 29 youth diagnosed with type 1 diabetes ages 6–15 years (mean age=11.72 years) receiving care at an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence and Wide Range Assessment of Memory and Learning. Independent samples t-tests were used to compare youth with T1D treated with MDI vs. CSII on glycemic control, verbal memory, visual memory, attention/concentration, and intelligence. Results: Mean intelligence scores for the insulin pump sample were higher than the daily injection sample. This difference was a medium to large effect. After controlling for demographic variables, age of onset for diabetes, and glycemic control, treatment type was still a significant predictor of intelligence demonstrating that CSII was associated with higher intelligence scores. Conclusion: The use of standardized measures of cognitive functioning in routine clinical care may shed some light on the complex interplay between cognitive functioning, treatment type, and glycemic control when managing pediatric patients with T1D.

Images in pediatric endocrinology

December 23, 2014

Benefit of testosterone in pediatric genital trauma

Mary White, Margaret Zacharin

Page range: 357-357

Original articles

September 11, 2014

Attenuated salivary cortisol response after exercise test in children with asthma

Ieteke Hiemstra, Sigrid M. Heijsman, Nicoline F. Koers, Gianni Bocca, Betty S. van der Veen, Nic J.G.M. Veeger, Arvid W.A. Kamps

Page range: 359-365

Abstract

Objective: The clinical relevance of lower basal cortisol levels in children with asthma is unclear. We compared the salivary cortisol response after a standardized exercise test in children with asthma versus the salivary cortisol response in healthy children. Methods: Nineteen prepubertal children with asthma and 20 prepubertal healthy children performed a standardized exercise test twice. Salivary cortisol levels were determined before exercise and immediately and 15 min after exercise. Morning salivary cortisol levels were determined from saliva collected at home. Results: Salivary cortisol levels increased in 84.2% of the healthy children compared to 35.0% in children with asthma after the 20-m shuttle-run test. Median increase in salivary cortisol levels was 200.3% [95% confidence interval (CI), 141.8–346.1] in healthy children compared to 89.8% (95% CI, 56.9–181.6) in children with asthma. The response was not related to the morning salivary cortisol level or maintenance dose of inhaled corticosteroids. The mean time to exhaustion of both shuttle-run tests was significantly shorter in children with asthma (mean difference 1.4 min; 95% CI, 0.7–2.3). None of the children had to stop because of dyspnea. Conclusion: Our study demonstrates that children with asthma using a maintenance dose of inhaled corticosteroids (ICS) have an attenuated salivary cortisol response compared with healthy children.

September 11, 2014

Reliability of pubertal maturation self-assessment in a school-based survey

Somchit Jaruratanasirikul, Piyawut Kreetapirom, Nattaporn Tassanakijpanich, Hutcha Sriplung

Page range: 367-374

Abstract

Aim: To assess the reliability of pubertal self-assessment of Thai adolescents. Subjects: Some 927 girls and 997 boys, aged 8–18 years, from nine schools in Hat-Yai municipality. Methods: The adolescents evaluated their pubertal status after being shown a line drawing of the five Tanner stages with a short description. Girls assessed their breast and pubic hair development, and boys assessed their pubic hair development. The pubertal self-assessments were compared to pubertal assessments made by a pediatrician who examined the children after their self-assessment. Kappa coefficient and percent agreement were used for statistical analysis. Results: The percent agreement of breast and pubic hair development between the girl’s self-assessments and the assessments by the pediatrician were 60.8% and 78%, respectively. Kappa coefficient for breast assessment was 0.50 (95% confidence interval, CI 0.47–0.53) and for pubic hair 0.68 (95% CI 0.65–0.72). Nearly 30% of girls aged younger than 10 years overestimated their breast development status while 45% of girls aged over 14 years underestimated their breast development (p<0.001). For boys, the percent agreement of pubic hair development between the adolescents and the pediatrician was 76.4%, with a weighted kappa coefficient of 0.68 (95% CI 0.65–0.72). Conclusion: Pubertal self-assessment using line drawings with a short description can be used as a reliable method to assess pubic hair maturation in boys and girls, but can be used with less reliability to assess the breast maturation in young girls.

October 25, 2014

Detection of inborn errors of metabolism using GC-MS: over 3 years of experience in southern China

MinYan Jiang, Li Liu, HuiFen Mei, XiuZhen Li, Jing Cheng, YanNa Cai

Page range: 375-380

Abstract

Background: Inborn errors of metabolism (IEM) have been detected worldwide using gas chromatography mass spectrometry (GC-MS) since the 1980s, but few related reports exist on the incidence, spectrum, and clinical presentation features of IEM in southern China. Method: From January 2009 to March 2012, 16,075 urine samples were collected from patients who were highly suspected of having IEM in Guangzhou Women and Children’s Medical Center. The specimens were evaluated using GC-MS. Results: We diagnosed 303 cases of IEM by urine GC-MS analysis, including 197 cases with amino acid disorders, 86 cases with organic acidurias (OAs), 10 cases with fatty acid oxidative (FAO) disorders, and 10 cases with peroxisomal disorders. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) was the most common (153 cases), followed by methylmalonic aciduria (48 cases), urea cycle disorders (21 cases), phenylketonuria (20 cases), propionic aciduria (11 cases), X-linked adrenoleukodystrophy (10 cases), multiple carboxylase deficiency (8 cases), glutaric aciduria type I (7 cases), isovaleric aciduria (6 cases), glutaric aciduria type II (4 cases), short-chain acyl-CoA dehydrogenase deficiency (4 cases), 3-hydroxy-3-methylglutaric aciduria (3 cases), maple syrup urine disease (2 cases), very long-chain acyl-CoA dehydrogenase deficiency (1 case), malonic aciduria (1 case), mevalonic aciduria (1 case), Canavan disease (1 case), lysine protein intolerance (1 case), and medium-chain acyl-CoA dehydrogenase deficiency (1 case). The clinical and laboratory features of IEM are neurologic signs, jaundice, metabolic acidosis, ketotic hypoglycemia, and hyperammonemia. Conclusion: In our study, GC-MS provided a diagnostic clue to OAs, amino acid disorders, FAO, and peroxisomal disorders. Urease pretreatment is useful for the diagnosis of NICCD. In southern China, the majority of IEM were amino acid disorders and organic acid disorders. FAO disorders were relatively rare, which we need to investigate further.

October 18, 2014

Assessing biological maturity: chronological age and the pubertal development scale predict free testosterone in adolescent males

Elizabeth E. Hibberd, Anthony C. Hackney, Amy R. Lane, Joseph B. Myers

Page range: 381-386

Abstract

Background: Pubertal development status has implications for development of physical characteristics, performance, and injury risk in school-aged athletes. Objective: The objective of this study was to evaluate the ability of non-invasive measures of biological maturity to predict salivary free testosterone. Participants: A total of 61 physically active males (ages 6–16) participated in this study. Methods: Participants had their anthropometrics measured, completed the Pubertal Development Scale (PDS), and reported their birthdays and the heights of their biological parents. Exact chronological age and percent of predicted height were calculated. Resting salivary samples were collected and assessed for free testosterone levels using enzyme-linked immunosorbent assay procedures. Variables were entered into a stepwise linear regression to predict free testosterone. Results: The regression model was statistically significant (R 2 =0.716, F 2,61 =74.2, p<0.005) with chronological age (β=0.66, t 60 =7.587, p<0.005) and PDS (β=0.26, t 60 =3.02, p=0.004) remaining as significant predictors of free testosterone. Conclusions: Chronological age and PDS adequately predict salivary free testosterone levels in school-aged males and may be an appropriate tool to evaluate physical maturity in school-aged males quickly, cheaply, and accurately.

December 16, 2014

Evaluation of puberty by verifying spontaneous and stimulated gonadotropin values in girls

Vivian L. Chin, Ziyong Cai, Leslie Lam, Bina Shah, Ping Zhou

Page range: 387-392

Abstract

Background: Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test. Objective: To determine the best predictive model for detecting puberty in girls. Subjects: Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15). Methods: Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed. Results: The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%. Conclusions: The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.

December 2, 2014

Longitudinal changes in C-reactive protein, proform of eosinophil major basic protein, and pregnancy-associated plasma protein-A during weight changes in obese children

Ulrik Lausten-Thomsen, Michael Gamborg, Christine Bøjsøe, Paula L. Hedley, Christian Munch Hagen, Michael Christiansen, Jens-Christian Holm

Page range: 393-398

Abstract

Background: Childhood obesity is associated with several complications, including cardiovascular comorbidity. Several biomarkers, such as high-sensitive C-reactive protein (hs-CRP), proform of eosinophil major basic protein (Pro-MBP) and pregnancy associated plasma protein-A (PAPP-A), have equally been linked to increased cardiovascular susceptibility. This study investigates these biomarkers during weight loss and regain in obese children. Materials and methods: A longitudinal study during a 12-week weight loss program with a 28 months follow-up was conducted. Anthropometrics and plasma concentrations of hs-CRP, Pro-MBP, and PAPP-A were measured at baseline; at days 14, 33 and 82 during weight loss; and at months 10, 16, and 28 during follow-up. Results: Fifty-three boys and 62 girls aged 8–15 years with a median body mass index (BMI) standard deviation score (SDS) at baseline of 2.78 (boys), and 2.70 (girls) were included. Ninety children completed the weight loss program and 68 children entered the follow-up program. Pro-MBP and PAPP-A, but not hs-CRP, exhibited individual-specific levels (tracking) during weight loss and regain. The PAPP-A/Pro-MBP correlation was strong, whereas the hs-CRP/PAPP-A correlation was weak during weight fluctuations. Conclusion: Hs-CRP changes reflect weight changes. PAPP-A and Pro-MBP exhibited tracking during weight perturbations and may contribute as early risk markers of cardiovascular susceptibility.

October 18, 2014

Caries in adolescents in relation to their skeletal status

Mikhail M. Kostik, Diana A. Kuzmina, Valeria P. Novikova, Valentina I. Larionova, Larisa A. Scheplyagina

Page range: 399-405

Abstract

Objective: Despite well-known evidence of association of caries with bone metabolic diseases, there are only a small number of studies about caries and bone mineral density (BMD) on pediatric population. We evaluated the possibility of bone mineralization and metabolism disturbances in children with caries and compared them with healthy individuals. Materials and methods: A total of 123 patients with caries (63 boys and 60 girls), aged 12–15 years, were included. The children were divided according caries stage: the decayed, missing, and filled tooth (DMFT) group (n=73) and the initial caries (IC) group (n=50), which have clinically active initial caries lesions on the enamel (“white spots”). Caries-free (CF) children (n=42) were the healthy controls. Bone mineralization was measured in all children with caries and healthy controls by dual-energy X-ray absorptiometry of the lumbar spine (L1–L4). For the assessment of bone metabolism, osteocalcin, carboxy terminal telopeptide of type I collagen (CTX), parathyroid hormone, Ca 2+ , inorganic phosphate, and total alkaline phosphatase were used. Results: Children with DMFT have low BMD and BMD Z score in association with low osteocalcin and high CTX levels, compared with IC (p=0.008 and p=0.0001, respectively) and CF children (p<0.0000 and p=0.0001, respectively). In DMFT, Ca 2+ was significantly higher compared with IC (p=0.01) and CF (p=0.003). Caries stages negatively correlated with BMD (r=–0.86, p<0.001). A differently directed correlation between CTX and osteocalcin was detected: CTX was negatively related to osteocalcin in the DMFT group (r=–0.22, p=0.043) and positively related in the IC (r=0.42, p=0.002) and CF children (r=0.58, p=0.0000). Conclusions: Children with any caries stage have decreased BMD accompanied with increased bone resorption. We consider that caries could be a marker of impact bone mineralization and metabolism.

November 6, 2014

Endothelial and metabolic disorders in adolescence: low birth weight is not an isolated risk factor

Priscila de Jesus dos Santos Alves, Ana Ciléia P.T. Henriques, Livia R.M. Pinto, Rosa Maria S. Mota, Carlos Henrique M. Alencar, Renata S. Alves, Francisco Herlânio C. Carvalho

Page range: 407-413

Abstract

Background: Low birth weight (LBW) seems to be a determining factor for many cardiovascular diseases in adult life. Objectives: The objectives of this study were to investigate the occurrence of metabolic syndrome (MetS) and endothelial dysfunction in adolescents with LBW and compare them with subjects with normal birth weights (NBW). Methods: This retrospective cohort study evaluated 172 adolescents (86 in each group) aged 10–20 years, who were born in a reference maternity hospital. The following criteria were adopted: International Diabetes Federation parameters for the diagnosis of MetS and flow-mediated brachial artery dilatation for endothelial dysfunction. Student’s t-test or Mann-Whitney tests were used for continuous variables (depending on the normality of distribution evaluated by the Shapiro-Wilk test), and the Fisher exact test was used for categorical variables. The significance level was determined at 0.05. Results: MetS was present in three cases of LBW and in four cases of NBW (p=0.70). The number of components of the syndrome was, on average, 0.6 and 0.5 in LBW and NBW, respectively (p=0.77). Endothelial dysfunction occurred in 25 (29.1%) cases of LBW and in 31 (36.1%) cases of NBW (p=0.33). Conclusion: LBW did not represent a risk factor in the occurrence of MetS or endothelial dysfunction in adolescence.

November 12, 2014

Comparison of cortisol samples in the first two weeks of life in preterm infants

Tiffany A. Moore, Kendra K. Schmid, Jeffrey A. French

Page range: 415-420

Abstract

Background: Growing literature on negative childhood stress emphasizes the need to understand cortisol values from varying biomarker samples. Objective: This work aimed to examine cortisol samples for usability, associations, and individual stability in neonates. Subjects: The sample consisted of preterm infants (n=31). Materials and methods: Analyses on cortisol collected from cord blood and from saliva and urine samples on days 1, 7, and 14 included Spearman correlations and paired t-tests. Results: Usability rates were 80.6% (cord blood), 85.9% (saliva), and 93.5% (urine). Salivary and urinary cortisol levels had significant correlation on day 1 only (p=0.004). Significant differences in individual stability of cortisol concentrations existed except in urine on days 1 and 7 and in saliva on days 7 and 14. Conclusions: Usability was highest for urine samples. We found little correlation between cortisol sample levels at each time; individual stability of cortisol concentrations was minimal. Interpretation of cortisol findings in all studies should be performed cautiously.

November 25, 2014

Mutations in BTD gene causing biotinidase deficiency: a regional report

Çiğdem Seher Kasapkara, Melek Akar, Mehmet Nuri Özbek, Heybet Tüzün, Bedri Aldudak, Rıza Taner Baran, Tijen Tanyalçın

Page range: 421-424

Abstract

Biotinidase deficiency is an autosomal recessive inborn error of biotin metabolism. Children with biotinidase deficiency cannot cleave biocytin and, therefore, cannot recycle biotin. Untreated individuals become secondarily biotin deficient, which in turn results in decreased activities of the biotin-dependent carboxylases and the subsequent accumulation of toxic metabolites causing clinical symptoms. Biotinidase deficiency is characterized by neurological, cutaneous manifestations and metabolic abnormalities. The worldwide incidence of profound biotinidase deficiency has been estimated at 1:112,271. The human biotinidase gene is located on chromosome 3p25 and consists of four exons with a total length of 1629 base pairs. To date, more than 100 mutations in the biotinidase gene known to cause biotinidase deficiency have been reported. The vast majority of mutations are homozygous or compound heterozygous. Finding known mutations can be correlated with the biochemical enzymatic results. This report summarizes the demographic features of patients identified as biotinidase deficient from August of 2012 through August of 2013 and mutation analysis results for 20 cases in the southeast region of Turkey.

Patient reports

October 18, 2014

Late-onset hypercalcemia in Williams-Beuren syndrome: importance of early and frequent screening and intervention

Alison M. Helfrich, Katherine Q. Philla

Page range: 425-428

Abstract

Williams-Beuren syndrome (WBS) affects multiple systems and has a known association with infantile hypercalcemia that is typically mild and transient. We report a 12-month-old female previously diagnosed with WBS by a chromosomal microarray, who was admitted for failure to thrive. Upon evaluation, serum calcium of 19.0 mg/dL (4.75 mmol/L) (normal 9–11 mg/dL, SI: 2.25–2.75 mmol/L) and serum ionized calcium of 2.33 mmol/L (normal 1.22–1.37 mmol/L) were revealed. Her hypercalcemia correlated with symptoms of irritability, poor feeding, mild hypotonia, and constipation, which were increasingly present for 6 months prior to admission. This calcium level is one of the highest reported in association with WBS. Additionally, while hypercalcemia associated with WBS typically resolves by the first year, this case represents a later presentation as compared to other reports. The patient initially responded to conservative treatment with intravenous fluids administration, loop diuretic therapy, and dietary calcium restriction. However, she subsequently had rebound hypercalcemia 5 weeks after treatment and received one dose of intravenous bisphosphonate with subsequent resolution of her hypercalcemia. Our report highlights the importance of screening, early management, and recognition of late presentation hypercalcemia in the setting of WBS.

September 11, 2014

Hepatoblastoma presenting as precocious puberty: a case report

Silvia Marino, Manuela Caruso, Gaetano Magro, Salvatore D’Amico, Milena La Spina, Carla Moscheo, Giovanna Russo, Andrea Di Cataldo

Page range: 429-432

Abstract

Hepatoblastoma (HB), a primary liver tumor in childhood, is often accompanied by alpha-fetoprotein (AFP) secretion, and sometimes by β-human chorionic gonadotropin hormone (β-hCG) secretion, and this can cause peripheral precocious puberty (PPP). We describe a case of PPP associated with HB. Laboratory tests showed an increase in AFP, β-hCG and testosterone values, and suppression of follicle-stimulating hormone and luteinizing hormone levels. After chemotherapy and surgery, AFP, β-hCG and testosterone levels normalized and signs of virilization did not progress further. The child did not show evidence for tumor recurrence after 16 months of follow-up. New therapeutic approaches and early diagnosis may ensure a better prognosis of virilizing HB, than reported in the past. Assessment of PPP should always take into account the possibility of a tumoral source.

September 11, 2014

Three cases of Wolfram syndrome with different clinical aspects

Emine Çamtosun, Zeynep Şıklar, Pınar Kocaay, Serdar Ceylaner, Sarah E. Flanagan, Sian Ellard, Merih Berberoğlu

Page range: 433-438

Abstract

Background: Wolfram syndrome is an autosomal recessive disorder caused by mutations in the WFS1 gene. Clinical heterogeneity has been reported both within and between families with WFS1 mutations. Subjects: The first case was diagnosed with insulin-dependent diabetes mellitus with positive for pancreatic autoantibodies and had a ketoacidotic attack in the follow-up period. The second case presented initially with optic atrophy and was diagnosed with behavioral and psychiatric problems at an early age. The third case had early onset insulin-dependent diabetes with multiple anomalies and congenital hypothyroidism. Many of these features have not been reported previously in patients with Wolfram syndrome. In all three patients homozygous mutations in WFS1 were identified. Conclusion: Wolfram syndrome is a disease where the characteristic features may present at different times. A diagnosis of Wolfram syndrome should therefore be considered even in the absence of the full spectrum of clinical features.

September 11, 2014

L-asparaginase induced hypoglycemia in a case of acute lymphoblastic leukemia: a patient report

Raiz Ahmad Misgar, Bashir Ahmad Laway, Sk Hammadur Rahaman, Arshad Iqbal Wani, Mir Iftikhar Bashir, Javeed Rasool Bhat

Page range: 439-441

Abstract

L-asparaginase (L-Asp) is an essential component of acute lymphoblastic leukemia (ALL) treatment protocols and its use has been associated with many adverse effects. We report a case of a 15-year-old boy with ALL who developed L-Asp induced hypoglycemia. To the best of our knowledge, only one such case has been reported previously.

October 11, 2014

Pyogenic granuloma, an unusual presentation of peripubertal vaginal bleeding. Case report and review of the literature

Alberto Barasoain-Millán, Francisco Javier Rodriguez-Contreras, Julio Guerrero-Fernandez, Maria Beato Merino, Isabel Gonzalez-Casado

Page range: 443-447

Abstract

Pyogenic granuloma, also named lobular capillary hemangioma, is a common proliferative vascular lesion known as a benign condition despite its rapid growth. It may appear in any cutaneous or mucosal surface but is usually restricted to the oral cavity. It is characterized by a friable mulberry-like lesion that can be sessile or pedunculated. Bleeding is usually its first clinical manifestation. Locations on respiratory, digestive and genital tracts are uncommon and sporadic. We describe the occurrence of an intravaginal pyogenic granuloma in a peripubertal girl with recurrent vaginal bleeding. This is the first reported case of a genital tract lobular capillary hemangioma in pediatric age to our knowledge. Therefore, we suggest this entity in the differential diagnosis of an unclear peripubertal vaginal bleeding.

October 11, 2014

Octreotide-associated cholestasis and hepatitis in an infant with congenital hyperinsulinism

Floris Levy-Khademi, Shchors Irina, Carmit Avnon-Ziv, Michal Levmore-Tamir, Oren Leder

Page range: 449-451

Abstract

Congenital hyperinsulinism (CHI) is the most common cause of prolonged hypoglycemia in the neonate. It is caused by several genetic mutations that interfere with the cascade of normal insulin secretion from pancreatic beta cells. Octreotide, a somatostatin analog, suppresses insulin secretion from pancreatic beta cells, and is an effective therapy used for both short and long term in the treatment of CHI. It is well tolerated in most patients; however, several adverse effects have been reported, most of them mild and transient. Impaired liver function has been described previously in few children. Here, we describe about a child with CHI treated with continuous intravenous octreotide who developed cholestasis and hepatitis after a short period of treatment. This combination of liver effects with a short duration of treatment has not been reported previously with octreotide use in this population.

August 12, 2014

Two novel mutations in the homogentisate-1,2-dioxygenase gene identified in Chinese Han Child with Alkaptonuria

Hongying Li, Kaihui Zhang, Qun Xu, Lixia Ma, Xin Lv, Ruopeng Sun

Page range: 453-456

Abstract

Alkaptonuria (AKU) is an autosomal recessive disorder of tyrosine metabolism, which is caused by a defect in the enzyme homogentisate 1,2-dioxygenase (HGD) with subsequent accumulation of homogentisic acid. Presently, more than 100 HGD mutations have been identified as the cause of the inborn error of metabolism across different populations worldwide. However, the HGD mutation is very rarely reported in Asia, especially China. In this study, we present mutational analyses of HGD gene in one Chinese Han child with AKU, which had been identified by gas chromatography-mass spectrometry detection of organic acids in urine samples. PCR and DNA sequencing of the entire coding region as well as exon-intron boundaries of HGD have been performed. Two novel mutations were identified in the HGD gene in this AKU case, a frameshift mutation of c.115delG in exon 3 and the splicing mutation of IVS5+3 A>C, a donor splice site of the exon 5 and exon-intron junction. The identification of these mutations in this study further expands the spectrum of known HGD gene mutations and contributes to prenatal molecular diagnosis of AKU.

August 12, 2014

Pituitary abscess in an adolescent girl: a case report and review of the literature

Ricardo Zegarra-Linares, Kathleen C. Moltz, Nahed Abdel-Haq

Page range: 457-462

Abstract

We report the case of a 15-year-old girl who presented with a history of recurrent bitemporal headaches for the last 2 months. In the prior few days, she complained of neck pain, emesis, phonophobia and photophobia, but no fever. Additional symptoms included polydipsia, polyuria and weight gain in the last year. Magnetic resonance imaging (MRI) of the brain demonstrated a cystic sellar and suprasellar mass with peripheral enhancement. Cerebrospinal fluid studies showed pleocytosis. Serum hormone levels were consistent with panhypopituitarism. Transnasal sphenoidotomy was performed, and 2 mL of purulent material was drained, confirming the diagnosis of pituitary abscess. The patient completed 6 weeks of parenteral antibiotics. She improved but continued to require home hormonal replacement therapy. A repeated MRI 3 months later showed abscess resolution. In addition to tumors, pituitary abscess should be considered in children who present with headache and panhypopituitarism, particularly in those who present with signs of meningeal inflammation. Prolonged parenteral antibiotics and surgical drainage are effective.

August 19, 2014

Neonatal thyrotoxicosis with severe supraventricular tachycardia: case report and review of the literature

Aslıhan Abbasoğlu, Ayşe Ecevit, Ali Ulaş Tuğcu, lkay Erdoğan, Sibel Tulgar Kınık, Aylin Tarcan

Page range: 463-466

Abstract

Neonatal thyrotoxicosis is a rare condition caused by the transplacental passage of thyroid stimulating immunoglobulins from mothers with Graves’ disease. We report a case of neonatal thyrotoxicosis with concurrent supraventricular tachycardia (SVT). The female infant, who was born by section due to breech delivery and meconium in the amniotic fluid at 36 weeks of gestation, presented with tachycardia on day 7. Her heart rate was between 260 and 300 beats/min, and an electrocardiogram revealed ongoing SVT. Sotalol was effective after two cardioversions in maintaining sinus rhythm. Thyroid function studies revealed hyperthyroidism in the infant, and her mother was found to have Graves’ disease. Since symptoms and signs can vary, especially in preterm infants with neonatal hyperthyroidism, we want to emphasize the importance of prenatal care and follow-ups of Graves’ disease associated pregnancies and management of newborns after birth.

August 15, 2014

Consumptive hypothyroidism associated with parotid infantile hemangioma

Federica De Corti, Carlo Crivellaro, Giovanni Franco Zanon, Claudia Luzzatto

Page range: 467-469

Abstract

Consumptive hypothyroidism is a rare condition usually described in association with diffuse infantile hemangioma of the liver, over-expressing type 3 iodothyronine-deiodinase. We report a case of acquired hypothyroidism associated with a parotid hemangioma in a male child, who was initially evaluated at 48 days of age due to persistent jaundice. Replacement hormonal therapy was promptly started, but resolution of the clinical and laboratory findings of hypothyroidism was only achieved at 3 months of age, when propranolol treatment was added to the therapeutic regimen. Our review of the literature retrieved only one case of proven consumptive hypothyroidism associated with a parotid infantile hemangioma, making a real incidence an underestimate: we believe one should consider this association a real possibility.

November 6, 2014

Novel mutations in the SLC25A13 gene in a patient with NICCD and severe manifestations

Hong Wang, Sainan Shu, Chen Chen, Zhihua Huang, DaoWen Wang

Page range: 471-475

Abstract

Neonatal intrahepatic cholestatic due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and characterized by neonatal/infantile-onset cholestatic hepatitis syndrome associated with conjugated hyperbilirubinemia and multiple aminoacidemias. We report the case of a Chinese female patient with NICCD disease who manifested prominent clinical features. The patient was diagnosed with NICCD based on cholestasis, aminoacidemia, and hypoproteinemia. She exhibited extreme aminoacidemia, coagulation disorders and untypical myocardial damage, which are rare in other NICCD patients genetically confirmed by us. This myocardial damage observed in obstructive jaundice could be caused by both hyperbilirubinemia and redundant blood bile acids. Screening the SLC25A13 gene revealed that this patient was compound heterozygous harboring two novel mutations, the c. 640C>T (p. Gln214X) in exon 7 and the c. 1709_1710insA (p. Ile570fs573X) in exon 16. Both mutations cause a premature stop codon and thereby truncated peptide or nonsense-mediated with loss of natural function accordingly. In conclusion, extremely manifested clinical features, including significant hyperbilirubinemia, multiple aminoacidemia, hypoproteinemia, coagulation disorders, and myocardial damage related to redundant blood bilirubin and bile acids, were observed in a NICCD patients with two novel mutations.

Short communications

November 22, 2014

Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia

Maja Stojiljkovic, Kristel Klaassen, Maja Djordjevic, Adrijan Sarajlija, Bozica Kecman, Milena Ugrin, Branka Zukic, Lourdes R. Desviat, Sonja Pavlovic, Belen Perez

Page range: 477-480

Abstract

Hyperphenylalaninemia (HPA) [phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiencies] is rare inborn metabolic disease characterized by elevated phenylalanine level in body fluids. In Serbia, 62 HPA patients have been identified through newborn screening since 1983. However, pterin pattern analysis is not performed. We present a patient initially diagnosed and treated as classical PKU. At 3 years of age, during infection with H1N1 influenza A virus, the patient first developed a neurologic crisis with encephalopathy and dystonic movements. We suspected that the patient is the first case of BH4 deficiency identified in Serbia. Genetic analyses showed that the patient does not have disease-causing variants of the PAH gene and carries a p.Asp136Val mutation in homozygous state in the PTS gene. For patients with treatable rare diseases, like PKU and BH4 deficiencies, correct diagnosis is crucial for the implementation of optimal treatment. If biochemical tests needed for differential diagnosis are not available, our experience emphasizes the necessity of immediate genetic testing after newborn screening.

About this journal

Objective
The aim of the Journal of Pediatric Endocrinology and Metabolism (JPEM) is to diffuse speedily new medical information by publishing clinical investigations in pediatric endocrinology and basic research from all over the world. JPEM is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups. JPEM is a high-quality journal dedicated to pediatric endocrinology in its broadest sense, which is needed at this time of rapid expansion of the field of endocrinology. JPEM publishes Reviews, Original Research, Case Reports, Short Communications and Letters to the Editor (including comments on published papers). JPEM publishes supplements of proceedings and abstracts of pediatric endocrinology and diabetes society meetings.

Topics

Pediatric endocrinology
Pediatric diabetes
Inherited metabolic diseases

Article formats

Original Research, Reviews, Mini Reviews, Opinion Papers, Case Report, Short Communications, Letters to the Editor (including comments on published papers)