Articles

Novel ways to monitor immunosuppression in pediatric kidney transplant recipients—underlying concepts and emerging data

After pediatric kidney transplantation, immunosuppressive therapy is given to avoid acute and chronic rejections. However, the immunosuppression causes an increased risk of severe viral complications and bacte...

Authors: Thurid Ahlenstiel-Grunow and Lars Pape

Aggressive infantile myofibromatosis with intestinal involvement

Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations...

Authors: Tristan Römer, Norbert Wagner, Till Braunschweig, Robert Meyer, Miriam Elbracht, Udo Kontny and Olga Moser

Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family

Ca²⁺ as a universal second messenger regulates basic biological functions including cell cycle, cell proliferation, cell differentiation, and cell death. Lack of the protein mitochondrial calcium uptake1 (MICU1),...

Authors: Fatemeh Bitarafan, Mehrnoosh Khodaeian, Elham Amjadi Sardehaei, Fatemeh Zahra Darvishi, Navid Almadani, Yalda Nilipour and Masoud Garshasbi

Daratumumab therapy for post-HSCT immune-mediated cytopenia: experiences from two pediatric cases and review of literature

Immune-mediated cytopenias (AIC) are challenging complications following allogeneic hematopoietic stem cell transplantation (HSCT). While broad-acting immunosuppressive agents like corticosteroids are often st...

Authors: Lina Driouk, Robert Schmitt, Anke Peters, Sabine Heine, Hermann Josef Girschick, Brigitte Strahm, Charlotte M. Niemeyer and Carsten Speckmann

Combined RT-qPCR and pyrosequencing of a Spike glycoprotein polybasic cleavage motif can uncover pediatric SARS-CoV-2 infections associated with heterogeneous presentation

Reverse transcription of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+)RNA genome and subgenomic RNAs (sgRNAs) and subsequent quantitative polymerase chain reaction (RT-qPCR) is the relia...

Authors: Patrick Philipp Weil, Jacqueline Hentschel, Frank Schult, Anton Pembaur, Beniam Ghebremedhin, Olivier Mboma, Andreas Heusch, Anna-Christin Reuter, Daniel Müller, Stefan Wirth, Malik Aydin, Andreas C. W. Jenke and Jan Postberg

Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity

Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels ...

Authors: Marta Ramon-Krauel, María Jesús Leal-Witt, Óscar Osorio-Conles, Montse Amat-Bou, Carles Lerin and David M. Selva

Molecular causes of congenital anomalies of the kidney and urinary tract (CAKUT)

Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 0.5–1/100 newborns and as a group they represent the most frequent cause for chronic kidney failure in children. CAKUT comprise clinically ...

Authors: Stefan Kohl, Sandra Habbig, Lutz T. Weber and Max C. Liebau

Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality

Epidermal development is a complex process of regulated cellular proliferation, differentiation, and tightly controlled cell death involving multiple cellular signaling networks. Here, we report a first descri...

Authors: Claudia Dafinger, Thomas Benzing, Jörg Dötsch, Bernhard Schermer and Max C. Liebau

Asprosin in pregnancy and childhood

Authors: Ruth Janoschek, Thorben Hoffmann, Yousef Ashraf Tawfik Morcos, Gerhard Sengle, Jörg Dötsch and Eva Hucklenbruch-Rother

Impact of early-life diet on long-term renal health

In the last years, great advances have been made in the effort to understand how nutritional influences can affect long-term renal health. Evidence has accumulated that maternal nutrition before and during pre...

Authors: Eva Nüsken, Jenny Voggel, Gregor Fink, Jörg Dötsch and Kai-Dietrich Nüsken

Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation ...

Authors: Gerhard Binder, Dirk Schnabel, Thomas Reinehr, Roland Pfäffle, Helmuth-Günther Dörr, Markus Bettendorf, Berthold Hauffa and Joachim Woelfle

Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency

Rare genetic variations in the leptin-melanocortin signalling pathway can severely impair appetite regulation and cause extreme obesity in early childhood.

Authors: Stefanie Zorn, Julia von Schnurbein, Katja Kohlsdorf, Christian Denzer and Martin Wabitsch

A case of recurrent herpes simplex 2 encephalitis, VZV reactivations, and dominant partial interferon-gamma-receptor-1 deficiency supports relevance of IFNgamma for antiviral defense in humans

Unlike infections with mycobacteria, reports of unusual viral infections in interferon-gamma-receptor (IFNγR) deficient patients are scarce. Therefore, discussion about increased susceptibility to viral infect...

Authors: Julia Körholz, Nicole Richter, Jochen Schäfer, Catharina Schuetz and Joachim Roesler

A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney

Glomerulonephritis results in a dysregulation of glomerular cells and may end up in chronic alterations and subsequent loss of renal function. Therefore, understanding mechanisms, which contribute to maintain ...

Authors: Ines Marek, Karl Friedrich Hilgers, Wolfgang Rascher, Joachim Woelfle and Andrea Hartner

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