TY  - JOUR
AB  - BACKGROUND/PURPOSE: MEGDHEL syndrome is a rare autosomal recessive metabolic disorder, which is characterized by 3-methylglutaconic aciduria with deafness-dystonia, hepatopathy, encephalopathy and Leigh-like syndrome. It is caused by biallelic pathogenic variants in the SERAC1 gene. Due to the unspecific symptoms and the diverse manifestations of the clinical phenotype, the diagnosis is challenging. Infantile MEGDHEL syndrome often has a severe disease course with acute liver failure. Differentiation from other metabolic disorders is difficult and requires a multidisciplinary approach. CASE PRESENTATION: A two-day-old small for gestational age neonate was admitted to our pediatric intensive care unit (PICU) due to severe liver failure with distinct hyperammonemia and hypoglycemia without elevation of transaminases or cholestasis. Due to high ammonia level, continuous hemodialysis was established immediately after admission. In addition, protein intake was stopped, and the patient anabolized with intravenous glucose. Temporary stabilization could be achieved after four days. In the further course, severe neurological and cardiocirculatory complications occurred, which ultimately led to the infant's death. In the metabolic diagnostics, a pronounced lactate acidosis and in urine an increased excretion of 3-methylglutaconic acid as well as other metabolites of mitochondrial energy metabolism has been the leading findings besides the hyperammonemia. Post-mortem trio whole genome analysis detected a homozygous pathogenic variant in SERAC1 with evidence of SERAC1 deficiency leading to the diagnosis of infantile MEGDHEL syndrome. CONCLUSION: When pediatricians are faced with hepatopathy or even acute liver failure without elevation of transaminases or cholestasis in newborns, SERAC1 deficiency should be considered as a potential differential diagnosis. The initial treatment is based on the recommended management of suspected metabolic disorders. Even while no cure is available yet, patients should be offered proper supportive management through a multidisciplinary team. In addition, genetic confirmation of the diagnosis is important for the families, especially regarding further family planning.If a newborn presents with hyperammonemia, hypoglycemia and impaired liver synthesis function without elevation of transaminases or cholestasis, the possible presence of MEGDHEL syndrome due to a SERAC1 mutation should be considered.
AU  - Kirchberg, I.*
AU  - Lainka, E.*
AU  - Gangfuß, A.*
AU  - Kuechler, A.*
AU  - Baertling, F.*
AU  - Schlieben, L.D.
AU  - Lenz, D.*
AU  - Tschiedel, E.*
C1  - 70182
C2  - 55446
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - Distinct neonatal hyperammonemia and liver synthesis dysfunction: Case report of a severe MEGDHEL syndrome.
JO  - Front. Pediatr.
VL  - 12
PB  - Frontiers Media Sa
PY  - 2024
SN  - 2296-2360
ER  - 

TY  - JOUR
AB  - INTRODUCTION: The COVID-19 pandemic with its containment measures such as closures of schools and daycare facilities led to numerous restrictions in daily life, putting developmental opportunities and health-related quality of life in children at risk. However, studies show that not every family was impacted equally by the pandemic and that this exceptional health and societal situation reinforced pre-existing health inequalities among the vulnerable. Our study aimed at analyzing changes in behavior and health-related quality of life of children attending elementary schools and daycare facilities in Bavaria, Germany in spring 2021. We also sought to identify associated factors contributing to inequalities in quality of life. METHODS: Data from a multi-center, open cohort study ("COVID Kids Bavaria") conducted in 101 childcare facilities and 69 elementary schools across all electoral districts of Bavaria were analyzed. Children attending these educational settings (aged 3-10 years) were eligible for participation in a survey on changes in behavior and health-related quality of life. The KINDLR questionnaire (based on children's self-report and parental report) was administered about one year after the onset of the pandemic (spring 2021). Descriptive and logistic regression analyses and comparisons to pre-pandemic KiGGS (German Health Interview and Examination Survey for Children and Adolescents) data were undertaken. RESULTS: Among respondents, a high percentage of parents reported changes in their children's eating and sleeping behavior, sports and outdoor activities as well as altered screen time. Health-related quality of life in KINDLR analyses compared to pre-pandemic population averages were lower in all age groups (for 3-6-year-old KINDLR-total score: COVID Kids Bavaria MD 74.78 ± 10.57 vs KiGGS data 80.0 ± 8.1; 7-10 years-old KINDLR-total score: COVID Kids Bavaria MD 73.88 ± 12.03 vs KiGGS data 79.30 ± 9.0). No significant differences were detected with regard to associated factors, namely type of institution, sex of the child, migration background, household size and parental education. CONCLUSION: These findings suggest a relevant impact of the COVID-19 pandemic on children's behavior and health-related quality of life one year after the onset of the pandemic. Further analyses in large-scale longitudinal studies are needed to determine the effects of specific pandemic or crisis associated factors contributing to health inequalities.
AU  - Schillok, H.*
AU  - Coenen, M.*
AU  - Rehfuess, E.A.*
AU  - Kuhlmann, P.H.*
AU  - Matl, S.*
AU  - Kindermann, H.*
AU  - Maison, N.
AU  - Eckert, J.*
AU  - von Both, U.*
AU  - Behrends, U.*
AU  - Frühwald, M.C.*
AU  - Neubert, A.*
AU  - Woelfle, J.*
AU  - Melter, M.*
AU  - Liese, J.*
AU  - Hübner, J.*
AU  - Klein, C.*
AU  - Kern, A.*
AU  - Jung-Sievers, C.*
C1  - 67896
C2  - 54374
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - Changes in behavior and quality of life in German young children during the COVID-19 pandemic-results from the COVID kids bavaria study.
JO  - Front. Pediatr.
VL  - 11
PB  - Frontiers Media Sa
PY  - 2023
SN  - 2296-2360
ER  - 

TY  - JOUR
AB  - We present a now 18-year-old female patient with a severe congenital myopathy phenotype, originally diagnosed as mitochondrial myopathy, however later revealed to constitute a SCN4A-related myopathy based on genetic testing. After birth, floppiness, bradycardia and respiratory insufficiency ensued, and moderately reduced mitochondrial complex I activity was found in muscle tissue (tested at 3 weeks and 3 years of age, respectively). She was treated with riboflavin, carnitine, creatine and a ketogenic diet. At the age of 13 years, whole exome sequencing challenged the initial diagnosis by identifying two (compound heterozygous) SCN4A variants affecting the highly conserved voltage sensor and pore regions of the voltage-gated sodium channel NaV1.4: a known pathogenic loss of function (LOF) variant [c.4360C>T; p.(Arg1454Trp)] and a novel variant of uncertain significance [c.3615C>G; p.(Asn1205Lys)]. For this novel variant, a LOF effect was predicted by in silico, clinical and functional evidence from paralog human sodium channels, and the variant was accordingly classified as likely pathogenic. The patient's phenotype is in line with the few published cases of autosomal recessive SCN4A-related myopathy. There was limited benefit from treatment with salbutamol and acetazolamide, while pyridostigmine caused side effects at a minor dose. This report highlights the importance of genetic testing in severe myopathies particularly in regard to treatment options and the value of paralog information in evaluating ion channel variations.
AU  - Berghold, V.M.*
AU  - Koko, M.*
AU  - Berutti, R.
AU  - Plecko, B.*
C1  - 66247
C2  - 52727
TI  - Case report: Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.
JO  - Front. Pediatr.
VL  - 10
PY  - 2022
SN  - 2296-2360
ER  - 

TY  - JOUR
AB  - Introduction: Here we report our results of a multi-center, open cohort study ("COVID-Kids-Bavaria") investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods: Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results: In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to <100/100,000 (OR = 10.3 [1.5-438], p < 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. Discussion: During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely.
AU  - Kern, A.*
AU  - Kuhlmann, P.H.*
AU  - Matl, S.*
AU  - Ege, M.*
AU  - Maison, N.
AU  - Eckert, J.K.*
AU  - von Both, U.*
AU  - Behrends, U.*
AU  - Anger, M.*
AU  - Frühwald, M.C.*
AU  - Gerstlauer, M.*
AU  - Woelfle, J.*
AU  - Neubert, A.*
AU  - Melter, M.*
AU  - Liese, J.*
AU  - Goettler, D.*
AU  - Sing, A.*
AU  - Liebl, B.*
AU  - Hübner, J.*
AU  - Klein, C.*
C1  - 65752
C2  - 52894
TI  - Surveillance of acute SARS-CoV-2 infections in elementary schools and daycare facilities in Bavaria, Germany (09/2020-03/2021).
JO  - Front. Pediatr.
VL  - 10
PY  - 2022
SN  - 2296-2360
ER  - 

TY  - JOUR
AB  - Background: Previous studies indicated preterm birth to be a risk factor for hypertension in adolescence and adulthood. However, studies in children investigating the underlying mechanisms are scarce. Objective: We hypothesized children born preterm to have higher excretion of cortisol and/or androgen metabolites per day concomitantly with higher blood pressure as compared to peers born at term. We thus aimed to compare urinary steroid profiles and blood pressure between 5- to 7-year-old children born preterm and peers born at term. Furthermore, aldosterone precursor excretion per day was compared between both groups. Methods: Blood pressure was measured in 236 children (preterms n = 116; gestational age 29.8 ± 2.6 (30; 24–33) weeks [mean ± standard deviation (median; range)]) using an automatic oscillometric device. Urinary steroid profiles were determined in 24-h urine samples (preterms n = 109; terms n = 113) using gas chromatographic-mass spectrometric analysis. To assess excretion of cortisol and androgen metabolites per day, major cortisol and androgen metabolites were summed, respectively. To assess aldosterone excretion per day tetrahydrocorticosterone, 5α-tetrahydrocorticosterone, and tetrahydro-11-deydrocorticosterone were summed. Results: Multiple regression analyses showed prematurity to be associated with systolic but not with diastolic blood pressure. When adjusted for potential confounders (prematurity, gender, age at day of examination, being born small for gestational age, breastfeeding, accelerated weight gain during infancy, family history of cardiovascular disease, parental hypertension, and body mass index) prematurity was shown to be associated with an increase in systolic blood pressure by 2.87 mmHg (95% confidence interval 0.48–5.27; p = 0.02). Cortisol, androgen metabolite, and aldosterone precursor excretion per day were not higher in individuals born preterm. In contrast to our hypothesis, multiple regression analysis showed prematurity to independently decrease cortisol and aldosterone precursor excretion per day (p < 0.001 and 0.04, respectively). Conclusion: This study provides further evidence for systolic blood pressure to be higher after preterm birth as early as at the age of 5 to 7 years. However, this seems not to be explained by elevated excretion of cortisol and/or androgen metabolites.
AU  - Landmann, E.*
AU  - Brugger, M.
AU  - Blank, V.*
AU  - Wudy, S.A.*
AU  - Hartmann, M.*
AU  - Strauch, K.
AU  - Rudloff, S.*
C1  - 63842
C2  - 51771
TI  - Adrenal steroid metabolism and blood pressure in 5- to 7-Year-old children born preterm as compared to peers born at term.
JO  - Front. Pediatr.
VL  - 9
PY  - 2021
SN  - 2296-2360
ER  - 

TY  - JOUR
AB  - The evidence for non-specific effects (NSE) of vaccinations on all-cause morbidity and mortality among children is growing. However, our understanding of the underlying mechanisms is still limited. One hypothesis is that NSE are mediated by antibody titers. We used data of 2,123 children from the population-based birth cohort study LISA conducted in Germany to explore whether routine childhood vaccinations and the individual infection history in the first 2 years of life are associated with unrelated antibody titers. We selected 19 exposures (infections and vaccinations) and investigated their association with levels of 12 IgG antibody titers at the age of 2 years. Based on univariable analyses (ANOVA), we identified 21 crude associations between exposures and titers (p < 0.05), while 11 (95%-CI: 6, 17) spurious associations were expected due to multiple testing. In exploratory multivariable analyses, we observed associations between seven investigated IgG titers and 10 exposures; either administered vaccines [e.g., higher anti-hRSV IgG titer in BCG-vaccinated children (regression-coefficient in standard-deviation-units: 0.38; 95%-CI: 0.12, 0.65)] or infections [e.g., higher anti-measles IgG titer in children with reported chickenpox (0.44; 95%-CI: 0.08, 0.80)]. Our results indicate the existence of associations between immunogenic exposures and unrelated antibody titers. Further studies investigating the underlying immunological mechanisms are required.
AU  - Caputo, M.*
AU  - Raupach-Rosin, H.*
AU  - Karch, A.*
AU  - Borte, M.*
AU  - Lehmann, I.*
AU  - Liebert, U.G.*
AU  - Standl, M.
AU  - Heinrich, J.
AU  - Mikolajczyk, R.T.*
C1  - 56536
C2  - 47088
CY  - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
TI  - Vaccinations and infections are associated with unrelated antibody titers: An analysis from the german birth cohort study LISA.
JO  - Front. Pediatr.
VL  - 7
PB  - Frontiers Media Sa
PY  - 2019
SN  - 2296-2360
ER  - 

TY  - JOUR
AB  - Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) represent the primary cause of chronic kidney disease in children. Many gene s have been attributed to the genesis of this disorder. Recently, haploinsufficiency of PBX1 caused by microdeletions has been shown to result in bilateral renal hypoplasia and other organ malformations. Materials and methods: Here, we report on a 14-year-old male patient with congenital bilateral dysplastic kidneys, cryptorchidism, hypoplastic clavicles, developmental delay, impaired intelligence, and minor dysmorphic features. Presuming a syndromic origin, we performed SNP array analysis to scan for large copy number variations (CNVs) followed by whole-exome sequencing (WES). Sanger sequencing was done to confirm the variant's de novo status. Results: SNP array analysis did not reveal any microdeletions or -duplications larger than 50 or 100 kb, respectively. WES identified a novel heterozygous 7-bp frameshift deletion in PBX1 (c.413_419del, p. Gly138Valfs*40) resulting in a loss-of-function. The de novo status could be confirmed by Sanger sequencing. Discussion: By WES, we identified a novel heterozygous de novo 7-bp frameshift deletion in PBX1. Our findings expand the spectrum of causative variants in PBX1-related CAKUT. In this case, WES proved to be the apt technique to detect the variant responsible for the patient's phenotype, as single gene testing is not feasible given the multitude of genes involved in CAKUT and SNP array analysis misses rare single-nucleotide variants and small Indels.
AU  - Riedhammer, K.M.*
AU  - Siegel, C.*
AU  - Alhaddad, B.*
AU  - Montoya, C.*
AU  - Kovács-Nagy, R.*
AU  - Wagner, M.
AU  - Meitinger, T.
AU  - Hoefele, J.*
C1  - 52485
C2  - 44013
CY  - Lausanne
TI  - Identification of a novel heterozygous de novo 7-bp frameshift deletion in PBX1 by whole-exome sequencing causing a multi-organ syndrome including bilateral dysplastic kidneys and hypoplastic clavicles.
JO  - Front. Pediatr.
VL  - 5
PB  - Frontiers Media Sa
PY  - 2017
SN  - 2296-2360
ER  -