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Abstract Objective To investigate the psychosocial burden in children and adolescents with juvenile rheumatic diseases during the COVID-19 pandemic. Methods As part of the multicentre observational KICK-COVID study linked to the National Pediatric Rheumatology Database, adolescents

Abstract Objective This study aims to elucidate the long‐term benefit of newborn screening (NBS) for individuals with long‐chain 3‐hydroxy‐acyl‐CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (MTP) deficiency, inherited metabolic diseases included in NBS programs worldwide. Methods German national multicenter study of individuals with confirmed LCHAD/MTP deficiency identified by NBS between 1999 and 2020 or selective metabolic screening. Analyses focused on NBS results, confirmatory diagnostics, and long‐term clinical outcomes. Results Sixty‐seven individuals with LCHAD/MTP deficiency were included in the study, thereof 54 identified by NBS. All screened individuals with LCHAD deficiency survived, but four with MTP deficiency (14.8%) died during the study period. Despite NBS and early treatment neonatal decompensations (28%), symptomatic disease course (94%), later metabolic decompensations (80%), cardiomyopathy (28%), myopathy (82%), hepatopathy (32%), retinopathy (17%), and/or neuropathy (22%) occurred. Hospitalization rates were high (up to a mean of 2.4 times/year). Disease courses in screened individuals with LCHAD and MTP deficiency were similar except for neuropathy, occurring earlier in individuals with MTP deficiency (median 3.9 vs. 11.4 years; p = 0.0447). Achievement of dietary goals decreased with age, from 75% in the first year of life to 12% at age 10, and consensus group recommendations on dietary management were often not achieved. Interpretation While NBS and early treatment result in improved (neonatal) survival, they cannot reliably prevent long‐term morbidity in screened individuals with LCHAD/MTP deficiency, highlighting the urgent need of better therapeutic strategies and the development of disease course‐altering treatment.

ObjectiveStudies have shown an increased incidence of pediatric type 1 diabetes during the COVID-19 pandemic, but the detailed role of SARS-CoV-2 infection in the incidence increase in type 1 diabetes remains unclear. We investigated the spatiotemporal association of pediatric type 1 diabetes and COVID-19 incidence at the district level in Germany.MethodsFor the period from March 2020 to June 2022, nationwide data on incident type 1 diabetes among children and adolescents aged

Abstract Background There is consistent evidence that the COVID-19 pandemic is associated with an increased psychosocial burden on children and adolescents and their parents. Relatively little is known about its particular impact on high-risk groups with chronic physical health conditions (CCs). Therefore, the primary aim of the study is to analyze the multiple impacts on health care and psychosocial well-being on these children and adolescents and their parents. Methods We will implement a two-stage approach. In the first step, parents and their underage children from three German patient registries for diabetes, obesity, and rheumatic diseases, are invited to fill out short questionnaires including questions about corona-specific stressors, the health care situation, and psychosocial well-being. In the next step, a more comprehensive, in-depth online survey is carried out in a smaller subsample. Discussion The study will provide insights into the multiple longer-term stressors during the COVID-19 pandemic in families with a child with a CC. The simultaneous consideration of medical and psycho-social endpoints will help to gain a deeper understanding of the complex interactions affecting family functioning, psychological well-being, and health care delivery. Trial registration German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

Objective: To investigate the frequency, treatment, and outcome of patients with diabetes due to severe insulin resistance syndromes (SIRS). Research Design and Methods: Based on data from the multicenter prospective Diabetes Registry DPV, we analyzed diagnosis, treatment, and outcome of 636,777 patients with diabetes from 1995 to 2022. Results: Diabetes due to SIRS was documented in 67 cases (62.7% females), 25 (37%) had lipodystrophies (LD) and 42 (63%) had congenital defects of insulin signaling. The relative frequency compared to type 1 diabetes (T1D) was about 1:2300. Median age at diabetes diagnosis in patients with SIRS was 14.8 years (interquartile range (IQR) 12.8–33.8). A total of 38 patients with SIRS (57%) received insulin and 34 (51%) other antidiabetics, mostly metformin. As high as 16% of patients with LD were treated with fibrates. Three out of eight patients with generalized LD (37.5%) were treated with metreleptin and one patient with Rabson–Mendenhall syndrome was treated with recombinant insulin-like growth factor 1. The median glycated hemoglobin level at follow-up was 7.1% (54 mmol/mol). Patients with LD had higher triglycerides than patients with T1D and T2D (P < 0.001 and P = 0.022, respectively), and also significantly higher liver enzymes and lower high-density lipoprotein cholesterol than patients with T1D (P < 0.001). Patients with insulin receptor disorders were significantly less likely to be treated with antihypertensive medication than patients with T2D (P = 0.042), despite having similar levels of hypertension. Conclusions: Diabetes due to SIRS is rarely diagnosed and should be suspected in lean children or young adults without classical T1D. Awareness of cardiovascular risk factors in these patients should be raised.

Abstract Background To provide estimates of the nationwide prevalence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in individuals younger than 20 years of age in Germany from 2002 to 2020 and to identify trends. Methods Data were obtained from the electronic health record “Diabetes Prospective Follow‐up Registry (DPV)” specific to diabetes care. Prevalence was estimated based on prevalent cases at the end of each year for the years 2002, 2008, 2014, and 2020 per 100 000 persons assuming a Poisson distribution and directly age‐ and/or sex‐standardized to the population in 2020. Individuals younger than 20 years of age with a clinical diagnosis of T1D or 10–19‐year‐olds with T2D were eligible for inclusion in the study. Results The standardized T1D prevalence per 100 000 persons was 138.9 (95% CI: 137.1; 140.6) in 2002 and 245.6 (243.1; 248.0) in 2020. The standardized T2D prevalence per 100 000 persons was 3.4 (3.1; 3.8) in 2002 and 10.8 (10.1; 11.5) in 2020. The annual percent change (APC) in prevalence declined over the three periods 2002–2008/2008–2014/2014–2020 (T1D: 6.3% [3.6%; 9.0%]/3.1% [0.7%; 5.5%]/0.5% [−1.7%; 2.85], T2D: 12.3% [5.3%; 20.8%]/4.7% [−0.6%; 10.3%]/3.0% [−1.8%; 8.0%]). From 2014 to 2020, the highest APCs were observed among 15–19‐year‐olds (T1D: 2.5% [1.3%; 3.6%], T2D: 3.4% [−0.5%; 7.5%]). Conclusions The increase in diabetes prevalence has slowed, but medical care should be prepared for an increase in adolescents with diabetes.

Abstract Background Data on patients with type 1 diabetes mellitus (T1DM) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections are sparse. This study aimed to investigate the association between SARS‐CoV‐2 infection and T1DM. Methods Data from the Prospective Diabetes Follow‐up (DPV) Registry were analyzed for diabetes patients tested for SARS‐CoV‐2 by polymerase chain reaction (PCR) in Germany, Austria, Switzerland, and Luxembourg during January 2020–June 2021, using Wilcoxon rank‐sum and chi‐square tests for continuous and dichotomous variables, adjusted for multiple testing. Results Data analysis of 1855 pediatric T1DM patients revealed no differences between asymptomatic/symptomatic infected and SARS‐CoV‐2 negative/positive patients regarding age, new‐onset diabetes, diabetes duration, and body mass index. Glycated hemoglobin A1c (HbA1c) and diabetic ketoacidosis (DKA) rate were not elevated in SARS‐CoV‐2‐positive vs. ‐negative patients. The COVID‐19 manifestation index was 37.5% in individuals with known T1DM, but 57.1% in individuals with new‐onset diabetes. 68.8% of positively tested patients were managed as outpatients/telemedically. Data analysis of 240 adult T1MD patients revealed no differences between positively and negatively tested patients except lower HbA1c. Of these patients, 83.3% had symptomatic infections; 35.7% of positively tested patients were hospitalized. Conclusions Our results indicate low morbidity in SARS‐CoV‐2‐infected pediatric T1DM patients. Most patients with known T1DM and SARS‐CoV‐2 infections could be managed as outpatients. However, SARS‐CoV‐2 infection was usually symptomatic if it coincided with new‐onset diabetes. In adult patients, symptomatic SARS‐CoV‐2 infection and hospitalization were associated with age.

Methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are very rare autosomal recessive inherited metabolic diseases from the group of organoacidopathies. Katabolism due to minor infections can lead to metabolic decompensation including hyperammonemia and ketoacidosis, especially in small children. We present data from a small cohort to clarify whether placement of a percutaneous endoscopic gastrostomy with jejunal tube (J-PEG) reduce metabolic imbalances and hospital stays. The aim is to prevent emergencies from occurring by preventing metabolic derailments at an early stage. 4 patients with MMA (N = 3) or PA (N = 1) were included. Data were collected at every investigation, in particular pH value, pCO2, bicarbonate, base excess, ammonia and lactate. Due to repeated metabolic derailments, a percutaneous endoscopic gastrostomy was placed for postpyloric nutrition. In conclusion, placement of a percutaneous endoscopic gastrostomy with postpyloric tube appears to reduce the rate of metabolic decompensations. In addition, hospital stays and especially the number of treatment days can be reduced. This method, especially the placement of a postpyloric tube could enable parents to prevent catabolism when vomiting begins by continuously feeding through the jejunal part, as a step to prevent a metabolic emergency from occurring.

This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (

Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation.