Journal of Pediatric Endocrinology and Metabolism

Published by De Gruyter

Volume 33 Issue 1

Issue of Journal of Pediatric Endocrinology and Metabolism

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Contents
Journal Overview

Publicly Available January 10, 2020

Editorial

January 10, 2020

Inborn errors of metabolism

Wieland Kiess, Anna Kirstein, Skadi Beblo

Page range: 1-3

Reviews

December 5, 2019

Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs)

Penelope D. Manta-Vogli, Kleopatra H. Schulpis, Yannis Dotsikas, Yannis L. Loukas

Page range: 5-20

Abstract

The establishment of expanded newborn screening (NBS) not only results in the early diagnosis and treatment of neonates with inborn errors of intermediary metabolism disorders (IEMDs) but also helps the affected females to reach the reproductive age under medical and dietetic support, as well as to give birth to normal infants. In this review, we aimed to focus on laboratory investigation tests, dietetic management and medical support for most known IEMD pregnant and lactating women, such as those suffering from aminoacidopathies, carbohydrate metabolic diseases and fatty acid (FAO) oxidation disorders.

December 19, 2019

The association between prenatal exposure to organochlorine compounds and neonatal thyroid hormone levels: a systematic review

Mahshid Gheidarloo, Roya Kelishadi, Silva Hovsepian, Mojtaba Keikha, Mahin Hashemipour

Page range: 21-33

Abstract

In this systematic review, the association between prenatal exposure to organochlorine pesticides (OCPs) and neonatal thyroid hormone levels was studied. A systematic search of scientific literature was performed from the PubMed, SCOPUS and ISI web of science electronic bibliographic databases. The search strategy for the review was [(organochlorine OR “organochlorine pesticides” OR “organochlorine pollutants” OR “organochlorine pollutant”) AND (“thyroid hormone” OR triiodothyronine OR Thyroxine OR “fetal thyroid function” OR “thyroid function” OR “Thyroid Stimulating Hormone” AND “prenatal” AND “maternal exposure”)] in English sources. In this review, 305 papers (PubMed: 30; Scopus: 29; ISI: 246) were identified through an electronic database search. Twenty-seven articles were assessed for eligibility, from which 16 qualified articles were selected for the final evaluation. The most common OCP metabolites which were evaluated in order were hexachlorobenzene (HCB) (13 studies), pp-dichlorodiphenyldichloroethylene (pp-DDE) (13 studies), hexachlorocyclohexane (HCH) (10 studies) and dichlorodiphenyltrichlorethane (DDT) (eight studies). A review of the documents related to the association of prenatal exposure of OCPs with fetal or neonatal thyroid function tests provides us with heterogeneous data in this field. Factors such as differences in the studied populations and their area, ethnic and genetic background, time and rate of exposure, possible interaction of other thyroid-disrupting environmental factors and dietary intake of micronutrients such as iodine and/or selenium are considered the main limitations for making an accurate conclusion. For some OCPs including DDT, DDE, HCH and HCB, there are supporting evidences, and it is suggested that their exposure could potentially alter the fetal thyroid function and consequently impair the neurodevelopment process of the infants.

Original Articles

December 10, 2019

Investigating the incidence rate and geographical distribution of congenital hypothyroidism among neonates in Isfahan province using geographic information system (GIS) between 2002 and 2015

Arezoo Karimi, Mahin Hashemipour, Khairollah Asadollahi, Salman Daliri

Page range: 35-45

Abstract

Background Congenital hypothyroidism (CH) is one of the main causes of mental retardation in neonates. The disease is associated with genetic, climatic and environmental factors. Accordingly, the present study was conducted to determine the incidence rate and correlation of geographic factors with CH in Isfahan province in order to explain the role of climatic factors in the incidence of disease in this province. Methods This cross-sectional study was conducted to determine the incidence rate and geographical distribution of CH in neonates born in the Isfahan province from the beginning of 2002 to the end of 2015. To estimate the geographic distribution, the ArcGIS software (version 10.3) was used and to investigate the relationship between geographical factors and CH, the Poisson regression test and dispersion diagrams were used. Data analysis was done using the SPSS16 software. Results According to the results of the screening of 1,006,404 neonates born in Isfahan, the mean incidence rate of CH in all infants was 2.3, and that in male and female infants was 2.39 and 2.2 per 1000 live births, respectively. There was a statistically significant correlation between the city of residence (p = 0.01), climatic conditions (p = 0.044), annual precipitation (p = 0.027), sunlight (p = 0.01) and CH. However, there was no significant relationship between the mean altitude above sea level (p = 0.6), land use (p = 0.4) and relative humidity (p = 0.24). Conclusions Based on the findings of this study, the incidence rate of CH in Isfahan province was higher than the average of the country. Moreover, among the geographical factors, climatic conditions, annual precipitation and sunlight were associated with CH.

December 19, 2019

Analysis of five cases of hypermethioninemia diagnosed by neonatal screening

Zhilei Zhang, Yanyun Wang, Dingyuan Ma, Wei Cheng, Yun Sun, Tao Jiang

Page range: 47-52

Abstract

Background Hypermethioninemia is a group of diseases with elevated plasma methionine (Met) caused by hereditary and non-hereditary factors, although it could also be caused by administration of the amino acid Met. Among these, the disease caused by methionine adenosyltransferase (MAT) I/III deficiency is the most common, and is characterized by persistent, isolated hypermethioninemia as well as slightly elevated homocysteine. S-adenosylmethionine is the product of Met, which can be used as a direct methyl donor of many substances, such as choline and nucleotide, and essential in the development of the body. Among the patients, most have no symptoms, and a small number have central nervous system complications with high levels of plasma Met, including mental retardation, cognitive impairment and special breathing odor. Methods In this study, five cases of MAT I/III deficiency were diagnosed and retrospectively analyzed among 220,000 newborns. Patients with high Met levels received a Met-restricted diet treatment. Results and conclusions MAT I/III deficiency is a common reason for Met elevation in neonatal screening by tandem mass spectrometry (MS/MS), which needs long-term follow-up except for these patients with explicitly benign mutations.

Open Access December 20, 2019

What is the evidence for beneficial effects of growth hormone treatment beyond height in short children born small for gestational age? A review of published literature

David Dunger, Feyza Darendeliler, Nurgun Kandemir, Mark Harris, Ali Rabbani, Anne-Marie Kappelgaard

Page range: 53-70

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Abstract

Background An increasing body of evidence supports the view that both an adverse intrauterine milieu and rapid postnatal weight gain in children born small for gestational age (SGA) contribute towards the risk for the development of chronic diseases in adult life. Content The aim of this review was to identify and summarize the published evidence on metabolic and cardiovascular risk, as well as risk of impaired cardiac function, intellectual capacity, quality of life, pubertal development and bone strength among children born SGA. The review will then address whether growth hormone (GH) therapy, commonly prescribed to reduce the height deficit in children born SGA who do not catch up in height, increases or decreases these risks over time. Summary Overall, there are limited data in support of a modest beneficial effect of GH therapy on the adverse metabolic and cardiovascular risk observed in short children born SGA. Evidence to support a positive effect of GH on bone strength and psychosocial outcomes is less convincing. Outlook Further evaluation into the clinical relevance of any potential long-term benefits of GH therapy on metabolic and cardiovascular endpoints is warranted.

December 7, 2019

Machine learning-based prediction of response to growth hormone treatment in Turner syndrome: the LG Growth Study

Mo Kyung Jung, Jeesuk Yu, Ji-Eun Lee, Se Young Kim, Hae Soon Kim, Eun-Gyong Yoo

Page range: 71-78

Abstract

Background Growth hormone (GH) treatment has become a common practice in Turner syndrome (TS). However, there are only a few studies on the response to GH treatment in TS. The aim of this study is to predict the responsiveness to GH treatment and to suggest a prediction model of height outcome in TS. Methods The clinical parameters of 105 TS patients registered in the LG Growth Study (LGS) were retrospectively reviewed. The prognostic factors for the good responders were identified, and the prediction of height response was investigated by the random forest (RF) method, and also, multiple regression models were applied. Results In the RF method, the most important predictive variable for the increment of height standard deviation score (SDS) during the first year of GH treatment was chronologic age (CA) at start of GH treatment. The RF method also showed that the increment of height SDS during the first year was the most important predictor in the increment of height SDS after 3 years of treatment. In a prediction model by multiple regression, younger CA was the significant predictor of height SDS gain during the first year (32.4% of the variability). After 3 years of treatment, mid-parental height (MPH) and the increment of height SDS during the first year were identified as significant predictors (76.6% of the variability). Conclusions Both the machine learning approach and the multiple regression model revealed that younger CA at the start of GH treatment was the most important factor related to height response in patients with TS.

December 13, 2019

Pathogenic/likely pathogenic variants in the SHOX, GHR and IGFALS genes among Indian children with idiopathic short stature

Anil Kumar, Vandana Jain, Madhumita Roy Chowdhury, Manoj Kumar, Punit Kaur, Madhulika Kabra

Page range: 79-88

Abstract

Background Our objective was to estimate the prevalence of pathogenic/likely pathogenic variants in the SHOX , GHR , and IGFALS genes among Indian children with idiopathic short stature (ISS), and assess the genotype-phenotype correlation. Methods We recruited 61 children with short stature, who were born appropriate for gestational age, had no obvious dysmorphism or disproportion, and in whom step-wise investigative work-up (including provocative growth hormone test) was normal. Multiplex ligation-dependent probe amplification was undertaken for identifying deletions/duplications in the SHOX gene. Bidirectional sequencing was performed for identifying variants in the SHOX and GHR genes in all, and for the IGFALS gene in those with serum insulin-like growth factor-1 (IGF-1) <−1 standard deviation. The genotype-phenotype correlation was studied. Results Four children (6.5%) had pathogenic heterozygous variants in the SHOX gene, with one child each having duplication of exon 5, splice site point variant c.278-1G > C in exon 3, partial deletion and complete deletion. None of the patients had pathogenic variants in the GHR gene. Of the 39 patients in whom the IGFALS gene was sequenced, novel heterozygous likely pathogenic variants were found in two children. One had the frameshift variant c.764_765insT, p.A265Gfs*114. The second had the missense variant c.1793G > A, p.R598H predicted by MutationTaster as ‘disease causing’, and indicated by the protein-modelling study as having compromised binding with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) due to altered conformation of the interacting loop. Conclusions Pathogenic variants in the SHOX and IGFALS genes account for a significant proportion of Indian children with ISS. Further molecular studies using next generation sequencing are needed to gain insight into pathophysiological mechanisms and effective treatment strategies for ISS.

December 5, 2019

Celiac disease in Saudi children with isolated short stature: is it rare or are we not screening rigorously enough?

Omar I. Saadah, Nouf M. ALNosani

Page range: 89-93

Abstract

Background Celiac disease (CeD) is an immune-mediated enteropathy induced by gluten exposure in individuals with genetic susceptibility. Short stature (SS) can be the sole clinical manifestation of CeD, in the absence of gastrointestinal (GI) symptoms. This study aimed to determine the prevalence of CeD in Saudi Arabian children with SS. Patients and methods Medical records were reviewed in a total number of 275 retrospective cases (during the period 2002–2014) of children with isolated SS from King Abdulaziz University Hospital, Jeddah. Their serum samples were tested with tissue transglutaminase (tTG) antibodies. Patients with a positive serology were scheduled for an upper endoscopy and intestinal biopsy to confirm CeD diagnosis before starting a gluten-free diet (GFD). Clinical, anthropometric and laboratory data were recorded for all patients. Results A total of 275 children with SS were included. The mean age ± standard deviation (SD) was 9.4 ± 4.0 years (range, 2.6–16.9 years) and males constituted the predominant gender group (151/275; 54.9%) over females (124/275; 45.1%). The mean ± SD height for age z score (HAZ) was −2.9 ± 1.0.Thirty-eight (13.8%) had positive serology, and 16 (5.8%) had biopsy-proven CeD. Apart from the difference in duration of delayed bone age between CeD patients and CeD-negative serology subjects (mean ± SD, 39.6 ± 10.5 vs. 18.6 ± 16.8, p = 0.02), no other major difference in other clinical or laboratory parameters was evident. Conclusions The prevalence rate of CeD in Saudi Arabian SS children was 5.8%, which is comparable to published reports of a number of other countries. Regular screening of children with SS is therefore justifiable.

December 7, 2019

The beneficial effect of psychological support on mothers with PKU children who suffer from social discrimination and damage of quality of life

Kostas Konstantinos Iakovou, Kleopatra Schulpis

Page range: 95-98

Abstract

Background Phenylketonuria (PKU) is a metabolic disorder of phenylalanine (phe) metabolism caused by the liver enzyme phe hydroxylase deficiency resulting in mental retardation. The only treatment for this disorder is the lifelong restriction of natural protein supplemented with phe-free amino acid formula. The aim of this study was to demonstrate the beneficial effect of psychological support in relation to the educational status on mothers with PKU children, who suffered from social discrimination (SD) and damage of quality of life (QLD). Methods A total number of 42 mothers with PKU children with a mean age of 26.8 years took part in this study. According to their educational status, they were divided into three groups: group a, primary school (n = 13); group b, high school (n = 15) and group c, university degree (n = 14). Psychological support was given once per week for 1 year. Results University degree mothers achieved the best results in ameliorating their symptoms and signs. Mothers who had completed high school felt a moderate amelioration of their SD and QL, whereas those who had finished primary school only felt a mild reduction of their symptoms. Educational status of the affected mothers should be always taken into account for the classification of the affected mothers into therapeutic groups. Familial and professional environment are very important for the success of psychological support. Conclusions Overall, the psychological support related to symptoms and signs of this metabolic disorder is in comparison with that in diabetic patients.

December 5, 2019

Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty

Dogus Vuralli, Zeynep Alev Ozon, Elmas Nazli Gonc, Ayfer Alikasifoglu, Nurgun Kandemir

Page range: 99-105

Abstract

Introduction Studies evaluating effects of gonadotropin-releasing hormone agonist (GnRHa) on weight and body-mass-index (BMI) in girls with idiopathic central precocious puberty (iCPP) include short-term effects. The aim of this study is to investigate changes in BMI during and 2 years after completion of GnRHa to determine the factors that may impact BMI in girls with iCPP. Methods Medical files of 138 girls who completed GnRHa were evaluated. All patients had weight and height measurements at the beginning and end of treatment, and 111 patients had anthropometric measurements 2 years after the completion of treatment. Results In the beginning, 82 (59.4%) had normal weight (NW), 42 (30.4%) were overweight (OW), and 14 (10.2%) were obese (OB). Analysis of BMI-standard deviation score (SDS) in the whole group showed an overall increase during GnRHa treatment (0.92 ± 0.74 vs. 1.20 ± 0.51, p < 0.001). Changes in BMI-SDS (ΔBMI-SDS) during GnRHa differed between NW and OW/OB (0.45 ± 0.31 vs. 0.03 ± 0.20, p < 0.001). BMI-SDSs of both groups returned to baseline scores (or initial levels) 2 years after the completion of treatment. Two factors affecting ΔBMI-SDS in multiple linear regression analyses were baseline BMI and Δheight-SDS, both correlated negatively with ΔBMI-SDS. Conclusions The present study is one of the studies evaluating BMI change over a long period of time in girls with CPP. Although BMI-SDS increased during GnRHa in NW girls, it was reversible in follow-up after treatment. However, BMI-SDS did not change during and in follow-up in OW/OB girls. Conserving BMI-SDS in OW/OB girls may be related to the fact that weight management programs were recommended for these patients. Dietary recommendations should be provided for children with NW who undergo GnRHa, as is the case for OW patients.

December 13, 2019

Sudden sex hormone withdrawal and the effects on body composition in late pubertal adolescents with gender dysphoria

Rahul Ghelani, Cheryl Lim, Caroline Brain, Mary Fewtrell, Gary Butler

Page range: 107-112

Abstract

Background Sex hormones initiate profound physical and physiological changes during the pubertal process, but to what extent are they responsible for continuing the body composition changes of late adolescence and what happens to body composition on sudden sex hormone withdrawal? Methods Thirty-six healthy, phenotypically and chromosomally normal late and post-pubertal individuals aged 15–17 years with gender dysphoria (transgirls – birth-registered males identifying as female n = 11; and transboys – birth-registered females identifying as male n = 25) underwent Tanita body composition analysis at 0, 6 and 12 months during reproductive hormone suppression with Triptorelin as part of the standard therapeutic protocol. Results and conclusions In the transgirl cohort, paired t-test analysis demonstrated a significant decrease in height and lean mass standard deviation scores over the 12-month period, going against an expected trajectory over that time. In contrast, oestrogen suppression appeared not to affect the body composition of transboys; their measurements were not significantly different at baseline and after 12 months of treatment. The withdrawal of sex hormone secretion does not appear to have a significant impact on female post-pubertal body composition, in contrast to that seen at the menopause. This suggests that other factors may preserve normal body balance in adolescents in the absence of sex steroids.

December 6, 2019

The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy

Nursel Muratoglu Sahin, Havva Nur Peltek Kendirci, Semra Çetinkaya, Şenay Savaş Erdeve, Zehra Aycan

Page range: 113-120

Abstract

Background Some studies have examined the effect of gonadal suppression on insulin-like growth factor-1 (IGF-1) levels and the growth velocity (GV) with conflicting results. Methods Forty-four girls treated with gonadotropin-releasing hormone analogue (GnRHa) for central precocious puberty (CPP) were included in the study. IGF-1 levels were examined at the beginning and after 12 months of treatment. Results IGF-1 and IGF-1 standard deviation score (SDS) according to chronological age (CA-IGF-1 SDS) at diagnosis were positively correlated with chronological age (CA), anthropometric measurements, stage of puberty, bone age (BA), BA-CA, follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, uterus length, endometrium thickness and ovarian volume (OV) at diagnosis (p < 0.05). There was no significant difference in IGF-1 levels after treatment. However, there was a negative correlation between ΔIGF-1 SDS and IGF-1 level, CA-IGF-1 SDS and BA-IGF-1 SDS at diagnosis (p < 0.05). There was no correlation between GV and IGF-1, ΔIGF-1. GV was negatively correlated with basal LH level at diagnosis (p = 0.008, r = −0.397). Peak LH levels of the patients who had GV-SDS < 0 were more suppressive than those of the patients who had GV-SDS > 0 after 12 months of treatment. Conclusions It was determined that the IGF-1 level and CA-IGF-1 SDS at baseline were correlated with more advanced pubertal stage prior to treatment. Initiation of treatment with a relatively high level of IGF-1 increased the risk of a decrease in the IGF-1 level. Likewise, the initiation of treatment with a relatively high LH level may increase the risk of low GV, but low GV was not related to the IGF-1 level. Increased sex steroid suppression may increase the risk of low GV.

December 19, 2019

BMI relationship to the onset of puberty: assessment of growth parameters and sexual maturity changes in Egyptian children and adolescents of both sexes

Soheir S. Abou El Ella, Naglaa Fathy Barseem, Maha A. Tawfik, Amira F. Ahmed

Page range: 121-128

Abstract

Background Puberty is the period of human growth and development. To determine the onset of puberty with regards to the effect of higher adiposity, together with growth parameters of the participants at various stages of sexual maturity for both sexes. Methods The study was conducted on 1944 children (8–16) years; 1022 girls (52.6%) and 922 boys (47.4%) were taken at random. Pubertal assessment was done using Tanner staging that assigned breast development in females and pubic and axillary hair in males and females. Testicular volume was recorded using a Prader orchidometer. Height, weight, body mass index (BMI), body mass (BM) fat, body fat percentage, through applying a body impedance analyzer, and others were recorded. Results The mean ages at the onset of puberty for females and males in our study were 10.29 ± 1.1 and 11.34 ± 1.02 years, respectively. Pubic hair (stage PH2) was attained at mean age of 10.72 ± 0.84 and 11.98 ± 1.03 years for females and males, respectively. For axillary hair (stage AH2), the mean age was 12.47 ± 0.68 years for females and 13.8 ± 0.58 years for males. The mean age at menarche was 12.41 ± 0.65 years. In concordance to BM fat and percentage, all pubertal stages started earlier in females with BMI ≥85th percentile comparable to females within average BMI. As for males, no significant relation was noted between mean pubertal ages and BMI values. Conclusions A significant association of mean ages of Tanner stages to excess weight especially in females warranted the increasing awareness about health care, nutritional aspects, and living circumstances.

December 9, 2019

The effects of a 12-week jump rope exercise program on body composition, insulin sensitivity, and academic self-efficacy in obese adolescent girls

Jun Kim, Won-Mok Son, Ronald J. Headid III, Elizabeth J. Pekas, John M. Noble, Song-Young Park

Page range: 129-137

Abstract

Background Childhood obesity is strongly associated with the development of cardiovascular disease (CVD). Exercise interventions have been used for obese children and adolescents to prevent the manifestation of CVD risks, such as hypertension and insulin resistance (IR). Additionally, obesity has been shown to be linked to low self-efficacy in adolescents, which has been shown to negatively impact academic performance. Therefore, the purpose of this study was to examine the effects of a 12-week jump rope exercise program on body composition, CVD risk factors, and academic self-efficacy (ASE) in obese adolescent girls with prehypertension. Methods Adolescent girls with prehypertension and obesity (n = 48, age 14–16 years) were randomly assigned to either the jump rope exercise group (EX, n = 24) or the control group (CON, n = 24). Body composition, blood pressure (BP), blood glucose, insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) (marker of IR), and ASE were assessed before and after 12 weeks of exercise training or control. Results There were significant group × time interactions following the 12-week exercise program for body fat percent, waist circumference (WC), systolic blood pressure (SBP), blood glucose, insulin levels, and HOMA-IR, which were all significantly reduced (p < 0.05). A significant improvement (p <0.05) was observed in task difficulty preference (TDP) and self-regulatory efficacy (SRE) following exercise training. Additionally, ASE was strongly correlated (r = −0.58) with body composition. Conclusions This study provides evidence that jump rope exercise intervention can be a useful therapeutic treatment to improve CVD risk factors and ASE in obese adolescent girls with prehypertension.

December 9, 2019

Onset of pituitary hormone deficiencies in optic nerve hypoplasia: a temporal trend analysis of 32 children at Mayo Clinic

Heather D. Wadams, Nidhi Gupta, Paul Novotny, Peter J. Tebben

Page range: 139-145

Abstract

Background The objective of this study was to evaluate the age at onset and frequency of individual pituitary hormone deficiencies (PHDs) in optic nerve hypoplasia (ONH). Methods We performed a retrospective chart review of patients ≤21 years of age evaluated between 1996 and 2014. Patients were included if they had: (1) ONH diagnosed by an ophthalmologist and/or magnetic resonance imaging (MRI), (2) documentation of pituitary hormone function on at least two separate occasions and (3) at least one PHD documented or a midline abnormality of the brain on MRI. Results Thirty-two patients (18 females, 14 males) were included (median age, 8 years [range, 1.1–21.0 years]). All patients had ONH (bilateral, n = 31; unilateral, n = 1) and at least one midline abnormality of the brain. At least one PHD was present in 75% of patients (n = 24). The remaining 25% of patients (n = 8) did not develop any PHD at least until the last follow-up (<2–8.6 years of follow-up), despite the presence of ONH and a midline abnormality of the brain. The median age (years) at diagnosis of antidiuretic hormone (ADH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and growth hormone (GH) deficiencies was 0.5, 0.6, 0.7 and 1.6, respectively. Twenty-three percent of all PHDs were identified during the neonatal period, 56% by 12 months and 72% by 36 months of age. The latest age at diagnosis of GH, ACTH and TSH deficiencies was 9.6, 9.9 and 12.6 years, respectively. Conclusions The majority of the PHDs in ONH develop within the first 3 years of life. We propose evaluation for endocrinopathies at the time of diagnosis of ONH, with repeat assessment for new deficiencies every 3–4 months until age 3 years and at least semi-annually until growth and puberty are complete.

December 16, 2019

Dietary practices in methylmalonic acidaemia: a European survey

Alex Pinto, Sharon Evans, Anne Daly, Manuela Ferreira Almeida, Murielle Assoun, Amaya Belanger-Quintana, Silvia Maria Bernabei, Sandra Bollhalder, David Cassiman, Helena Champion, Heidi Chan, Karen Corthouts, Jaime Dalmau, Foekje de Boer, Corinne De Laet, An de Meyer, An Desloovere, Alice Dianin, Marjorie Dixon, Katharina Dokoupil, Sandrine Dubois, Francois Eyskens, Ana Faria, Ilaria Fasan, Elisabeth Favre, François Feillet, Anna Fekete, Giorgia Gallo, Cerys Gingell, Joanna Gribben, Kit Kaalund Hansen, Nienke Ter Horst, Camille Jankowski, Renske Janssen-Regelink, Ilana Jones, Catherine Jouault, Gudrun Elise Kahrs, Irene Kok, Agnieszka Kowalik, Catherine Laguerre, Sandrine Le Verge, Alessandra Liguori, Rina Lilje, Cornelia Maddalon, Doris Mayr, Uta Meyer, Avril Micciche, Ulrike Och, Martine Robert, Júlio César Rocha, Hazel Rogozinski, Carmen Rohde, Kathleen Ross, Isabelle Saruggia, Andrea Schlune, Kath Singleton, Elisabeth Sjoqvist, Rachel Skeath, Linn Helene Stolen, Allyson Terry, Corrie Timmer, Lyndsey Tomlinson, Alison Tooke, Kristel Vande Kerckhove, Esther van Dam, Dorine van den Hurk, Liesbeth van der Ploeg, Marleen van Driessche, Margreet van Rijn, Annemiek van Wegberg, Carla Vasconcelos, Helle Vestergaard, Isidro Vitoria, Diana Webster, Fiona White, Lucy White, Heidi Zweers, Anita MacDonald

Page range: 147-155

Abstract

Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providing sufficient energy to avoid catabolism and to limit production of methylmalonic acid. The goal is to achieve normal growth, good nutritional status and the maintenance of metabolic stability. Aim To describe the dietary management of patients with MMA across Europe. Methods A cross-sectional questionnaire was sent to European colleagues managing inherited metabolic disorders (IMDs) (n=53) with 27 questions about the nutritional management of organic acidaemias. Data were analysed by different age ranges (0–6 months; 7–12 months; 1–10 years; 11–16 years; >16 years). Results Questionnaires were returned from 53 centres. Twenty-five centres cared for 80 patients with MMA vitamin B12 responsive (MMAB12r) and 43 centres managed 215 patients with MMA vitamin B12 non-responsive (MMAB12nr). For MMAB12r patients, 44% of centres (n=11/25) prescribed natural protein below the World Health Organization/Food and Agriculture Organization/United Nations University (WHO/FAO/UNU) 2007 safe levels of protein intake in at least one age range. Precursor-free amino acids (PFAA) were prescribed by 40% of centres (10/25) caring for 36% (29/80) of all the patients. For MMAB12nr patients, 72% of centres (n=31/43) prescribed natural protein below the safe levels of protein intake (WHO/FAO/UNU 2007) in at least one age range. PFAA were prescribed by 77% of centres (n=33/43) managing 81% (n=174/215) of patients. In MMAB12nr patients, 90 (42%) required tube feeding: 25 via a nasogastric tube and 65 via a gastrostomy. Conclusions A high percentage of centres used PFAA in MMA patients together with a protein prescription that provided less than the safe levels of natural protein intake. However, there was inconsistent practices across Europe. Long-term efficacy studies are needed to study patient outcome when using PFAA with different severities of natural protein restrictions in patients with MMA to guide future practice.

Case Reports

December 6, 2019

Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13

Melis Demir Köse, Mehtap Kagnici, Taha Reşit Özdemir, Cahit Barış Erdur, Gülin Erdemir, Miray Karakoyun, Yiğit Guzin, Serdar Ceylaner, Ferah Genel

Page range: 157-163

Abstract

Background Citrin deficiency (CD) is an autosomal recessive genetic disorder caused by a defect in the mitochondrial aspartate/glutamate antiporter, citrin. Three clinical manifestations have been described until today. Case presentation We reported 5 CD patients from two families. Four patients were male and one patient was female. Two of them have NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency); three of them have CTLN2 (adult-onset type II citrullinemia). Both NICCD patients showed typical clinical and biochemical changes with a diagnosis confirmed by mutations in the SLC25A13 gene. We detected a previously unreported homozygous novel mutation c.478delC (L160Wfs*36 ) on the SLC25A13 gene. All of the CTLN2 patients were siblings. Proband was a 15-year-old mentally retarded and autistic male who had admitted to our emergency with disorientation. Laboratory data showed hyperammonemia and citrullinemia. Conclusions Two different profiles of age-related CD have been depicted with this article. It has been aimed to underline that the CD can be observed in different forms not only in neonatals or little infants but also in adolescents. This article is the first case series that covers both NICCD and CTLN2 cases together and that has been published in Turkey. Considering the fact that especially the majority of CTLN2 cases have been identified in Asian countries, our article has vital importance in terms of defining phenotypic features of the disease.

December 10, 2019

A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation

Asburce Olgac, Ülkühan Öztoprak, Çiğdem Seher Kasapkara, Mustafa Kılıç, Deniz Yüksel, Emine Betül Derinkuyu, Yasemin Taşçı Yıldız, Serdar Ceylaner, Fatih Süheyl Ezgu

Page range: 165-170

Abstract

Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9 . A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.

December 5, 2019

Sinusitis, an under-reported adverse effect in children treated with radioactive iodine therapy and review of the current literature

Elizabeth T. Walsh, Janel D. Hunter, David F. Crudo, Cathrine Constantacos

Page range: 171-173

Abstract

Background Radioactive iodine (RAI) therapy is prevalent in the treatment of Graves’ disease. Adverse effects in pediatrics are not well-described. Case presentation A 13-year-old female underwent RAI therapy for Graves’ disease. Eight days later, she developed facial pain and forehead burning. She was diagnosed with sinusitis and started on pseudoephedrine with resolution in 24 h. Conclusions She endured prolonged discomfort due to an under-recognized adverse effect of RAI. Studies identify the nose as a site of RAI accumulation and smaller nasal passages may predispose children to sinusitis. We report the first pediatric case of sinusitis following RAI. With the increasing use of RAI to treat Graves’ disease, clinicians must recognize this adverse effect.

Publicly Available December 24, 2019

Acknowledgment

Page range: 175-177

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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)

Volume 33 Issue 1

Issue of Journal of Pediatric Endocrinology and Metabolism

Frontmatter

Inborn errors of metabolism

Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs)

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The beneficial effect of psychological support on mothers with PKU children who suffer from social discrimination and damage of quality of life

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The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy

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The effects of a 12-week jump rope exercise program on body composition, insulin sensitivity, and academic self-efficacy in obese adolescent girls

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Onset of pituitary hormone deficiencies in optic nerve hypoplasia: a temporal trend analysis of 32 children at Mayo Clinic

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Dietary practices in methylmalonic acidaemia: a European survey

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Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13

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A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation

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Sinusitis, an under-reported adverse effect in children treated with radioactive iodine therapy and review of the current literature

Abstract

Acknowledgment