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Defects in steroid biosynthesis in adrenals and gonads lead to complex and profound clinical consequences that can be grouped in four categories: (1) defects of salt–water homeostasis and sexual development (DSD), (2) defects of salt–water homeostasis, (3) defects of sexual development, and (4) end-organ steroid hormone resistance. Among the members of the first group, lipoid adrenal hyperplasia is characterized by lack of all steroid hormones, with consequent 46, XY DSD and salt loss in the first weeks of life. 17a-Hydroxylase deficiency leads also to 46, XY DSD associated with hypertension and hypokalemia. 3b-Hydroxysteroid dehydrogenase deficiency causes incomplete virilization in male fetuses, together with salt loss. 21-Hydroxylase deficiency, whose nonclassic form is one of the most common autosomal recessive diseases in humans, is responsible for female ambiguous genitalia at birth and salt loss. 11b-Hydroxylase deficiency differs from 21-hydroxylase deficiency for the absence of salt wasting and later presence of hypertension and hypokalemia. Defects of P450 oxidoreductase, a cofactor common to 21-hydroxylase, 17a-hydroxylase, and aromatase, lead to a complex combined defect of all three enzymes.

Objective To investigate whether the medical interview in the pediatric context generates a stressful response in parents in form of heightened cortisol activity, and whether pediatricians’ empathetic communication is able to attenuate this stress response. Methods 68 parents were recruited at pediatric out-patient and in-patient consultations. Salivary samples were collected between 60 and 30 min prior to the consultation, shortly before the consultation, 20 min as well as 45 min after the consultation. 19 pediatricians participated in the study and effectuated the medical visit as usual. We videotaped the consultations and coded pediatricians’ affective communication using the RIAS and the Four Habits Coding Scheme. Results Parents’ cortisol increased during the medical visit with a peak at 20 min after the medical encounter. Furthermore, multilevel analysis revealed a lesser increase in parents’ cortisol response associated with pediatricians’ levels in supportive communication behaviors. Conclusion As indicated by their humoral stress responses, the medical encounter was stressful for the parents. Pediatricians’ affective communication modulated this stress response in that more supportive communication was related to smaller cortisol increases. Practice implication Pediatricians’ affective communication behavior during the medical visit can alleviate parents’ distress and anxiety, representing a source of social and emotional support.

IntroductionThere is compositional overlap between the maternal intestinal microbiome, the breast milk microbiome and the infant oral and intestinal microbiome. Antibiotics cause profound changes in the microbiome. However, the effect of intrapartum and early-life antibiotics on the maternal intestinal and breast milk microbiome, and the infant oral and intestinal microbiome, and whether effects are only short term or persist long term remain uncertain.Methods and analysesIn this prospective cohort study, we will use metagenomic sequencing to determine: (1) the effect of intrapartum antibiotics on the composition of the breast milk, and the infant oral and intestinal microbiome, including the development and persistence of antibiotic resistance; (2) the effect of antibiotic exposure in the first year of life on the composition of the infant oral and intestinal microbiome, including the development and persistence of antibiotic resistance; (3) the effect of disruption of the infant oral and intestinal microbiome on health outcomes and (4) the compositional overlap between the maternal intestinal microbiome, the breast milk microbiome and the infant oral and intestinal microbiome.Ethics and disseminationThe ABERRANT study has been approved by the commission cantonale d’éthique de la recherche sur l’être humain (CER-VD) du Canton de Vaud (#2019–01567). Outcomes will be disseminated through publication and will be presented at scientific conferences.Trial registration numberNCT04091282.

Tyrosine hydroxylase catalyses the hydroxylation of L-tyrosine to l-DOPA, the rate-limiting step in the synthesis of catecholamines. Mutations in the TH gene encoding tyrosine hydroxylase are associated with the autosomal recessive disorder tyrosine hydroxylase deficiency, which manifests phenotypes varying from infantile parkinsonism and DOPA-responsive dystonia, also termed type A, to complex encephalopathy with perinatal onset, termed type B. We generated homozygous Th knock-in mice with the mutation Th-p.R203H, equivalent to the most recurrent human mutation associated with type B tyrosine hydroxylase deficiency (TH-p.R233H), often unresponsive to l-DOPA treatment. The Th knock-in mice showed normal survival and food intake, but hypotension, hypokinesia, reduced motor coordination, wide-based gate and catalepsy. This phenotype was associated with a gradual loss of central catecholamines and the serious manifestations of motor impairment presented diurnal fluctuation but did not improve with standard l-DOPA treatment. The mutant tyrosine hydroxylase enzyme was unstable and exhibited deficient stabilization by catecholamines, leading to decline of brain tyrosine hydroxylase-immunoreactivity in the Th knock-in mice. In fact the substantia nigra presented an almost normal level of mutant tyrosine hydroxylase protein but distinct absence of the enzyme was observed in the striatum, indicating a mutation-associated mislocalization of tyrosine hydroxylase in the nigrostriatal pathway. This hypomorphic mouse model thus provides understanding on pathomechanisms in type B tyrosine hydroxylase deficiency and a platform for the evaluation of novel therapeutics for movement disorders with loss of dopaminergic input to the striatum. Fil: Korner, Germaine. Universitat Zurich; Suiza. The Children´s Research Centre; Suiza. Neuroscience Center Zurich; Suiza Fil: Noain, Daniela. Universitat Zurich; Suiza Fil: Ying, Ming. University Of Bergen; Noruega Fil: Hole, Magnus. University Of Bergen; Noruega Fil: Flydal, Marte I.. University Of Bergen; Noruega Fil: Scherer, Tanja. Universitat Zurich; Suiza. The Children´s Research Centre;; Suiza Fil: Allegri, Gabriella. Universitat Zurich; Suiza. The Children´s Research Centre; Suiza Fil: Rassi, Anahita. Universitat Zurich; Suiza Fil: Fingerhut, Ralph. University Children´s Hospital; Suiza Fil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Pillai, Samyuktha. Universitat Zurich; Suiza Fil: Wueest, Stephan. The Children’s Research Centre ; Suiza. Universitat Zurich; Suiza Fil: Konrad, Daniel. Swiss Federal Institute Of Technology Zurich; Suiza Fil: Lauber Biason, Anna. University of Fribourg; Suiza Fil: Baumann, Christian R.. Neuroscience Centre Zurich ; Suiza Fil: Bindoff, Laurence A. University of Fribourg; Suiza Fil: Martinez, Aurora. University Of Bergen; Noruega Fil: Beat, Thony. Universitat Zurich; Suiza. Neuroscience Centre Zurich ; Suiza. he Children’s Research Centre ; Suiza

We describe three male children from a Bedouin clan, two of whom are siblings, who have various degrees of incomplete virilization due to isolated 17,20-lyase deficiency. The patients have low (basal and post ACTH or hCG stimulation) plasma testosterone and androstenedione levels. An abnormally high plasma 17-hydroxyprogesterone concentration was detected. A favorable response following local testosterone administration was seen in two patients. Surprisingly, an unexplained flat cortisol response to ACTH test was also noted. Although no biochemical model can yet adequately explain the impairment in cortisol response to ACTH in these patients, it seems prudent to take this lack of cortisol response into consideration. We therefore recommend hydrocortisone supplement during moderate to severe stress.