Articles

Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis ca...

Authors: Nami Mohammadian Khonsari, Sahar Mohammad Poor Nami, Benyamin Hakak-Zargar and Tessa Voth

Early clinical course after hematopoietic stem cell transplantation in children with juvenile metachromatic leukodystrophy

Long-term outcomes of hematopoietic stem cell transplantation (HSCT) in children with juvenile metachromatic leukodystrophy (MLD) have been investigated systematically, while short-term effects of HSCT on the ...

Authors: Judith Beschle, Michaela Döring, Christiane Kehrer, Christa Raabe, Ute Bayha, Manuel Strölin, Judith Böhringer, Andrea Bevot, Nadja Kaiser, Benjamin Bender, Alexander Grimm, Peter Lang, Ingo Müller, Ingeborg Krägeloh-Mann and Samuel Groeschel

Nup133 and ERα mediate the differential effects of hyperoxia-induced damage in male and female OPCs

Hyperoxia is a well-known cause of cerebral white matter injury in preterm infants with male sex being an independent and critical risk factor for poor neurodevelopmental outcome. Sex is therefore being widely...

Authors: Donna Elizabeth Sunny, Elke Hammer, Sebastian Strempel, Christy Joseph, Himanshu Manchanda, Till Ittermann, Stephanie Hübner, Frank Ulrich Weiss, Uwe Völker and Matthias Heckmann

Osteogenesis imperfecta—pathophysiology and therapeutic options

Osteogenesis imperfecta (OI) is a rare congenital disease with a wide spectrum of severity characterized by skeletal deformity and increased bone fragility as well as additional, variable extraskeletal symptom...

Authors: Julia Etich, Lennart Leßmeier, Mirko Rehberg, Helge Sill, Frank Zaucke, Christian Netzer and Oliver Semler

Genotype-phenotype correlations in children and adolescents with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by mutations in the active 21-hydroxylase gene (CYP21A2). The clinical symptoms can vary greatly. To date, no systematic s...

Authors: Helmuth-Günther Dörr, Nadja Schulze, Markus Bettendorf, Gerhard Binder, Walter Bonfig, Christian Denzer, Desiree Dunstheimer, Kirsten Salzgeber, Heinrich Schmidt, Karl Otfried Schwab, Egbert Voss, Martin Wabitsch and Joachim Wölfle

DNA methylation biomarkers of future health outcomes in children

Biomarkers which predict future health outcomes are key to the goals of precision health. Such biomarkers do not have to be involved in the causal pathway of a disease, and their performance is best assessed u...

Authors: Shivanthan Shanthikumar, Melanie R. Neeland, Jovana Maksimovic, Sarath C. Ranganathan and Richard Saffery

Infant formula with cow’s milk fat and prebiotics affects intestinal flora, but not the incidence of infections during infancy in a double-blind randomized controlled trial

The postnatal intestinal colonization of human milk-fed and formula-fed infants differs substantially, as does the susceptibility to infectious diseases during infancy. Specific ingredients in human milk, such...

Authors: Antonia Nomayo, Andreas Schwiertz, Rainer Rossi, Katharina Timme, Janine Foster, Richard Zelenka, Josef Tvrdik and Frank Jochum

Pro-inflammatory cytokine ratios determine the clinical course of febrile neutropenia in children receiving chemotherapy

Febrile neutropenia is a common and serious complication during treatment of childhood cancer. Empirical broad-spectrum antibiotics are usually administered until neutrophil cell count recovery. It was the aim...

Authors: Mira Siegmund, Julia Pagel, Tasja Scholz, Jan Rupp, Christoph Härtel and Melchior Lauten

Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring

To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm...

Authors: M. R. Alcorta-García, C. N. López-Villaseñor, G. Sánchez-Ferrer, H. Flores-Mendoza, F. Castorena-Torres, M. A. Aguilar-Torres, C. M. Sepúlveda-Treviño, J. A. Hernández-Hernández, R. C. López-Sánchez and V. J. Lara-Díaz

Shedding light on pediatric diseases: multispectral optoacoustic tomography at the doorway to clinical applications

Optoacoustic imaging (OAI), or photoacoustic imaging (PAI), has fundamentally influenced basic science by providing high-resolution visualization of biological mechanisms. With the introduction of multispectra...

Authors: Adrian P. Regensburger, Alexandra L. Wagner, Jing Claussen, Maximilian J. Waldner and Ferdinand Knieling

Random X chromosome inactivation in patients with Klinefelter syndrome

X chromosome inactivation (XCI) is an indispensable process in the development of human female embryos. Reportedly, XCI occurs when a blastocyst contains 10–12 embryonic progenitor cells. To date, it remains u...

Authors: Kenichi Kinjo, Tomoko Yoshida, Yoshitomo Kobori, Hiroshi Okada, Erina Suzuki, Tsutomu Ogata, Mami Miyado and Maki Fukami

Shaping of the nephron – a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney

The impairment of nephrogenesis is caused by noxae, all of which are significantly different in molecular composition. These can cause an early termination of nephron development in preterm and low birth weigh...

Authors: Will W. Minuth

Functional analysis of granulocyte and monocyte subpopulations in neonates

Neonate immune cell functions lack full protection against pathogens. This could be either defect or protective mechanism against overshooting proinflammatory immune responses.

Authors: Ines Hegge, Ferry Niepel, Anja Lange, Antje Vogelgesang, Matthias Heckmann and Johanna Ruhnau

Vegetarian diets in childhood and adolescence

In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whethe...

Authors: Silvia Rudloff, Christoph Bührer, Frank Jochum, Thomas Kauth, Mathilde Kersting, Antje Körner, Berthold Koletzko, Walter Mihatsch, Christine Prell, Thomas Reinehr and Klaus-Peter Zimmer

Vitamin D supplementation after the second year of life: joint position of the Committee on Nutrition, German Society for Pediatric and Adolescent Medicine (DGKJ e.V.), and the German Society for Pediatric Endocrinology and Diabetology (DGKED e.V.)

Low vitamin D serum concentrations have been associated with rickets and other disorders in observational studies. Since vitamin D serum concentrations in children and adolescents are frequently below referenc...

Authors: Thomas Reinehr, Dirk Schnabel, Martin Wabitsch, Susanne Bechtold-Dalla Pozza, Christoph Bührer, Bettina Heidtmann, Frank Jochum, Thomas Kauth, Antje Körner, Walter Mihatsch, Christine Prell, Silvia Rudloff, Bettina Tittel, Joachim Woelfle, Klaus-Peter Zimmer and Berthold Koletzko

Complementary foods in baby food pouches: position statement from the Nutrition Commission of the German Society for Pediatrics and Adolescent Medicine (DGKJ, e.V.)

Pureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young c...

Authors: Berthold Koletzko, Christoph Bührer, Regina Ensenauer, Frank Jochum, Hermann Kalhoff, Burkhard Lawrenz, Antje Körner, Walter Mihatsch, Silvia Rudloff and Klaus-Peter Zimmer

KUNO-Kids birth cohort study: rationale, design, and cohort description

Birth cohort studies can contribute substantially to the understanding of health and disease — in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various asp...

Authors: Susanne Brandstetter, Antoaneta A. Toncheva, Jakob Niggel, Christine Wolff, Silvia Gran, Birgit Seelbach-Göbel, Christian Apfelbacher, Michael Melter and Michael Kabesch

Gene correction of HBB mutations in CD34⁺ hematopoietic stem cells using Cas9 mRNA and ssODN donors

β-Thalassemia is an inherited hematological disorder caused by mutations in the human hemoglobin beta (HBB) gene that reduce or abrogate β-globin expression. Although lentiviral-mediated expression of β-globin an...

Authors: Justin S. Antony, Ngadhnjim Latifi, A. K. M. Ashiqul Haque, Andrés Lamsfus-Calle, Alberto Daniel-Moreno, Sebastian Graeter, Praveen Baskaran, Petra Weinmann, Markus Mezger, Rupert Handgretinger and Michael S. D. Kormann

Chemotherapy and the pediatric brain

Survival rates of children with cancer are steadily increasing. This urges our attention to neurocognitive and psychiatric outcomes, as these can markedly influence the quality of life of these children. Neuro...

Authors: Chrysanthy Ikonomidou

The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases

S100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, ...

Authors: Dirk Holzinger, Dirk Foell and Christoph Kessel

Precision medicine in pediatric oncology

Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and ...

Authors: Stefan E. G. Burdach, Mike-Andrew Westhoff, Maximilian Felix Steinhauser and Klaus-Michael Debatin

Anti-inflammatory monocytes—interplay of innate and adaptive immunity

Monocytes are central to our health as they contribute to both hemispheres of our immune system, the innate and the adaptive arm. Sensing signals from the outside world, monocytes govern the innate immunity by...

Authors: Georg Varga and Dirk Foell

Intrauterine growth restriction - impact on cardiovascular diseases later in life

Intrauterine growth restriction (IUGR) is a fetal pathology which leads to increased risk for certain neonatal complications. Furthermore, clinical and experimental studies revealed that IUGR is associated wit...

Authors: Carlos Menendez-Castro, Wolfgang Rascher and Andrea Hartner

The potential of antisense oligonucleotide therapies for inherited childhood lung diseases

Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target a...

Authors: Kelly M. Martinovich, Nicole C. Shaw, Anthony Kicic, André Schultz, Sue Fletcher, Steve D. Wilton and Stephen M. Stick

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility

Impaired regulatory T cell immunity plays a central role in the development of type 1 diabetes (T1D). Interleukin-2 receptor (IL-2R) signaling is essential for regulatory T cells (T_REG), and cytokine-inducible SH...

Authors: Julia Seyfarth, Heinz Ahlert, Joachim Rosenbauer, Christina Baechle, Michael Roden, Reinhard W. Holl, Ertan Mayatepek, Thomas Meissner and Marc Jacobsen

Preserved in vitro immunoreactivity in children receiving long-term immunosuppressive therapy due to inflammatory bowel disease or autoimmune hepatitis

Children with inflammatory bowel disease (IBD) or autoimmune hepatitis (AIH) are at risk for severe infections. This is partially a result of their chronic disease condition but, moreover, a side effect of the...

Authors: Teresa Schleker, Eva-Maria Jacobsen, Benjamin Mayer, Gudrun Strauss, Klaus-Michael Debatin and Carsten Posovszky

Concepts for a therapeutic prolongation of nephrogenesis in preterm and low-birth-weight babies must correspond to structural-functional properties in the nephrogenic zone

Numerous investigations are dealing with anlage of the mammalian kidney and primary development of nephrons. However, only few information is available about the last steps in kidney development leading at bir...

Authors: Will W. Minuth

The BPD trio? Interaction of dysregulated PDGF, VEGF, and TGF signaling in neonatal chronic lung disease

The development of neonatal chronic lung disease (nCLD), i.e., bronchopulmonary dysplasia (BPD) in preterm infants, significantly determines long-term outcome in this patient population. Risk factors include m...

Authors: Prajakta Oak and Anne Hilgendorff

Estimated prevalence of potentially damaging variants in the leptin gene

Mutations in the leptin gene (LEP) can alter the secretion or interaction of leptin with its receptor, leading to extreme early-onset obesity. The purpose of this work was to estimate the prevalence of heteroz...

Authors: Adriana Nunziata, Guntram Borck, Jan-Bernd Funcke, Katja Kohlsdorf, Stephanie Brandt, Anke Hinney, Barbara Moepps, Peter Gierschik, Klaus-Michael Debatin, Pamela Fischer-Posovszky and Martin Wabitsch

Transcatheter atrial septal defect closure in an infant (body weight 6.4 kg) using the GORE CARDIOFORM septal occluder (GCSO)

Transcatheter closure has become the treatment of choice for secundum atrial septal defects (ASD II), but particularly in small children, there is concern regarding procedure-related complications.

Authors: Roman Scheidmann, Thomas Paul and Matthias Sigler

Autism spectrum disorder and Li-Fraumeni syndrome: purely coincidental or mechanistically associated?

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with impaired social interactions and communication and restrictive, repetitive patterns of behaviors, interests, and activities. A recent epid...

Authors: Michaela Kuhlen, Julia Taeubner, Dagmar Wieczorek and Arndt Borkhardt

The molecular pathophysiology of chronic non-bacterial osteomyelitis (CNO)—a systematic review

Chronic non-bacterial osteomyelitis (CNO) belongs to the growing spectrum of autoinflammatory diseases and primarily affects the skeletal system. Peak onset ranges between 7 and 12 years of age. The clinical s...

Authors: Sigrun Ruth Hofmann, Franz Kapplusch, Katrin Mäbert and Christian Michael Hedrich

Pediatric precursor B acute lymphoblastic leukemia: are T helper cells the missing link in the infectious etiology theory?

Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infect...

Authors: Simone Bürgler and David Nadal

Abstracts of the 52nd Workshop for Pediatric Research

Authors: Rhea van den Bruck, Patrick P. Weil, Thomas Ziegenhals, Philipp Schreiner, Stefan Juranek, Daniel Gödde, Silvia Vogel, Frauke Schuster, Valerie Orth, Johannes Dörner, Daniel Pembaur, Meike Röper, Stefan Störkel, Hubert Zirngibl, Stefan Wirth, Andreas C. W. Jenke…

Human perinatal immunity in physiological conditions and during infection

The intrauterine environment was long considered sterile. However, several infectious threats are already present during fetal life. This review focuses on the postnatal immunological consequences of prenatal ...

Authors: Gijs T. J. van Well, Leonie A. Daalderop, Tim Wolfs and Boris W. Kramer

Role of second-hand smoke (SHS)-induced proteostasis/autophagy impairment in pediatric lung diseases

Exposure to second-hand tobacco smoke (SHS) is one of the prime risk factors for chronic lung disease development. Smoking during pregnancy may lead to birth defects in the newborn that include pulmonary dysfu...

Authors: Neel Patel, Christopher D. Trumph, Manish Bodas and Neeraj Vij

Renal consequences of preterm birth

The developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viabilit...

Authors: Amelie Stritzke, Sumesh Thomas, Harish Amin, Christoph Fusch and Abhay Lodha

Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients

Cystic fibrosis (CF) is a genetic disease in which bacterial infections of the airways play a major role in the long-term clinical outcome. In recent years, a number of next-generation sequencing (NGS)-based s...

Authors: Sébastien Boutin and Alexander H. Dalpke

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

The pathological course of several chronic inflammatory diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid arthritis, features an aberrant innate immune response dominat...

Authors: Camilla Margaroli and Rabindra Tirouvanziam

Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evid...

Authors: Pamela Millar-Büchner, Amber R. Philp, Noemí Gutierrez, Sandra Villanueva, Bredford Kerr and Carlos A. Flores

Wilms’ tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes

Wilms’ tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor ...

Authors: Patricia Midori Murobushi Ozawa, Carolina Batista Ariza, Roberta Losi-Guembarovski, Alda Losi Guembarovski, Carlos Eduardo Coral de Oliveira, Bruna Karina Banin-Hirata, Marina Okuyama Kishima, Diego Lima Petenuci and Maria Angelica Ehara Watanabe

Leukocyte recruitment in preterm and term infants

Impaired cellular innate immune defense accounts for susceptibility to sepsis and its high morbidity and mortality in preterm infants. Leukocyte recruitment is an integral part of the cellular immune response ...

Authors: Katinka Karenberg, Hannes Hudalla and David Frommhold

Linking bronchopulmonary dysplasia to adult chronic lung diseases: role of WNT signaling

Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in infants caused by pre- and/or postnatal lung injury. BPD is characterized by arrested alveolarization and vascularization due...

Authors: Chiharu Ota, Hoeke A. Baarsma, Darcy E. Wagner, Anne Hilgendorff and Melanie Königshoff

Transient spontaneous remission in congenital MLL-AF10 rearranged acute myeloid leukemia presenting with cardiorespiratory failure and meconium ileus

Neonatal leukemia is a rare disease with an estimated prevalence of about one to five in a million neonates. The majority being acute myeloid leukemia (AML), neonatal leukemia can present with a variety of sym...

Authors: Tobias Gyárfás, Juergen Wintgens, Wolfgang Biskup, Ilske Oschlies, Wolfram Klapper, Reiner Siebert, Susanne Bens, Claudia Haferlach, Roland Meisel, Michaela Kuhlen and Arndt Borkhardt

The experience of canakinumab in renal amyloidosis secondary to Familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited recurrent attacks of fever and serositis. Patients may develop renal amyloidosis. Colchicine prevents attacks ...

Authors: Betul Sozeri, Nesrin Gulez, Malik Ergin and Erkin Serdaroglu

Molecular biology of the gut

Authors: Hassan Y. Naim, Klaus-Peter Zimmer and Buford Nichols

Early origins of asthma (and allergy)

Asthma is the most common chronic disease starting in childhood and persisting into adulthood in many cases. During childhood, different forms of asthma and wheezing disorders exist that can be discriminated b...

Authors: Michael Kabesch

Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia—a new therapeutic strategy?

Influenza viruses (IVs) circulate seasonally and are a common cause of respiratory infections in pediatric and adult patients. Additionally, recurrent pandemics cause massive morbidity and mortality worldwide....

Authors: Barbara Rösler and Susanne Herold

Vitamin A-retinoid signaling in pulmonary development and disease

Retinoic acid (RA), the active form of vitamin A, regulates key developmental processes in multiple organs. In the developing lung, RA is crucial for normal growth and differentiation of airways. Disruption in...

Authors: Hector A. Marquez and Wellington V. Cardoso

The puzzle of immune phenotypes of childhood asthma

Asthma represents the most common chronic childhood disease worldwide. Whereas preschool children present with wheezing triggered by different factors (multitrigger and viral wheeze), clinical asthma manifesta...

Authors: Katja Landgraf-Rauf, Bettina Anselm and Bianca Schaub