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Introduction: The care of children and adolescents in need of care at home is exacerbated by the shortage of skilled workers in the care sector, which leads to bottlenecks in care and presents caring families with major challenges. The implementation of new care approaches in existing structures in the healthcare system is proving to be a key development task in order to provide targeted support for affected families in the future., Methods: Qualitative explorative interview study to record the perspective of families with (seriously) ill children and adolescents on the current care situation and possible helpful support services. The sampling was criteria-driven and the analysis and evaluation was content-analytical. Respondents were given a short questionnaire to record socio-demographic characteristics., Results: In particular, the transmission of the diagnosis, the everyday challenges and the impact on quality of life were named as stress factors by n=10 participating parents. Improved access to information, voluntary structures and central contact points as well as digital services were named as key development needs., Conclusion: The interviews from real life and needs-oriented perspective show that there is a need to expand low-threshold care coordination services, strengthen voluntary structures and use telemedical services. Meeting these needs should enable access to specialized treatment and helpful services, especially in rural areas., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The CSF1R gene, located on chromosome 5, encodes a 108 kDa protein and plays a critical role in regulating myeloid cell function. Mutations in CSF1R have been identified as a cause of a rare white matter disease called adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP, also known as CSF1R-related leukoencephalopathy), characterized by progressive neurological dysfunction. This study aimed to broaden the genetic basis of ALSP by identifying novel CSF1R variants in patients with characteristic clinical and imaging features of ALSP. Genetic analysis was performed through whole-exome sequencing or panel analysis for leukodystrophy genes. Variant annotation and classification were conducted using computational tools, and the identified variants were categorized following the recommendations of the American College of Medical Genetics and Genomics (ACMG). To assess the evolutionary conservation of the novel variants within the CSF1R protein, amino acid sequences were compared across different species. The study identified six previously unreported CSF1R variants (c.2384G>T, c.2133_2919del, c.1837G>A, c.2304C>A, c.2517G>T, c.2642C>T) in seven patients with ALSP, contributing to the expanding knowledge of the genetic diversity underlying this rare disease. The analysis revealed considerable genetic and clinical heterogeneity among these patients. The findings emphasize the need for a comprehensive understanding of the genetic basis of rare diseases like ALSP and underscored the importance of genetic testing, even in cases with no family history of the disease. The study's contribution to the growing spectrum of ALSP genetics and phenotypes enhances our knowledge of this condition, which can be crucial for both diagnosis and potential future treatments., (© 2024. The Author(s).)

Context: The condition when a person's gender identity does not match the sex assigned at birth is called gender incongruence (GI). Numbers of GI people seeking medical care increased tremendously over the last decade. Diabetes mellitus is a severe and lifelong disease. GI combined with diabetes may potentiate into a burdensome package for affected people., Objective: The study aimed to characterize people with GI and diabetes from an extensive standardized registry, the Prospective Diabetes Follow-up Registry (DPV), and to identify potential metabolic and psychological burdens., Methods: We compared demographic and clinical registry data of persons with type 1 or type 2 diabetes and GI to those without GI and used propensity score matching (1:4) with age, diabetes duration and treatment year as covariates., Results: 75 persons with GI, 49 with type 1 and 26 with type 2 diabetes were identified. HbA1c values were similar in matched persons with type 1 or 2 diabetes and GI compared to those without GI. Lipid profiles showed no difference, neither in type 1 nor in type 2 diabetes. Diastolic blood pressure was higher in the type 1 and GI group than in those without, whereas systolic blood pressure showed comparable results in all groups. Depression and anxiety were significantly higher in GI people (type 1 and 2). Non-suicidal self-injurious behaviour was more common in type 1 and GI, as was suicidality in type 2 with GI., Conclusion: Mental health issues are frequent in people with diabetes and GI and need to be specially addressed in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer HB declared a shared affiliation with the author(s) MF to the handling editor at the time of review., (Copyright © 2024 Boettcher, Tittel, Reschke, Fritsch, Schreiner, Achenbach, Thiele-Schmitz, Gillessen, Galler, Nellen-Hellmuth, Golembowski and Holl.)

Aim: To examine the time trends and factors associated with the onset of puberty in children with type 1 diabetes (T1D) using data from the German Diabetes Prospective Follow-up (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry., Methods: A total of 13 127 children with T1D, aged 6 to 18 years, were included in the analysis. Regression analysis was performed to investigate the relationship between diabetes duration, body mass index (BMI) standard deviation score (SDS), glycated haemoglobin (HbA1c) level, migration background, and the onset of puberty, stratified by sex., Results: Our findings revealed a significant trend towards earlier puberty in both girls and boys with T1D over the observed period (2000 to 2021). Puberty onset in girls (thelarche Tanner stage B2) decreased from 11.48 (11.35-11.65) years in 2000 to 10.93 (10.79-11.08) years in 2021 and gonadarche (Tanner stage G2/testicular volume >3 mL) decreased from 12.62 (12.42-12.82) years in 2000 to 11.98 (11.79-12.16) years in 2021 in boys (both P < 0.001). Longer diabetes duration, higher BMI SDS, and lower HbA1c level were associated with earlier puberty in both sexes (P < 0.001)., Conclusions: Our study highlights earlier puberty in children with T1D, influenced by BMI SDS, HbA1c level, and migration background. This has important implications for diabetes management and supporting healthy development. Further research is needed to understand the underlying mechanisms and develop potential interventions for this vulnerable population., (© 2023 John Wiley & Sons Ltd.)

Objective: Little is known about specific cutaneous findings in children and adolescents with overweight and obesity. This study assessed the association of skin signs with pivotal auxological and endocrinological parameters and their influence on the quality of life (QoL) of young people with obesity., Study Design: All patients initially recruited for a tertiary hospital's weight control program were offered participation in this interdisciplinary, single-center, cross-sectional study. All participants underwent a detailed dermatological examination, anthropometric measurements and laboratory examinations. QoL was assessed with validated questionnaires., Results: A total of 103 children and adolescents (age 11.6 ±2.5 years, 41% female, 25% prepubertal, BMI SDS 2.6 ± 0.5, homeostatic model assessment (HOMA) score 3.3 ± 4.2; mean ± s.d.) were recruited in a 12-month study period. Skin affections were linearly associated with increasing BMI and higher age. The most common skin findings were (%) striae distensae (71.0), keratosis pilaris (64.7), acanthosis nigricans (45.0), acne vulgaris (39.2), acrochordons (25.5) and plantar hyperkeratosis (17.6). The HOMA score was associated with acanthosis nigricans (P = 0.047), keratosis pilaris (P = 0.019) and acne vulgaris (P < 0.001). The general mean QoL(QoL) score, as assessed by the WHO-5, was 70 out of 100. A total of 38.9% of participants reported impaired dermatological QoL., Conclusions: This study shows the high prevalence of skin lesions in children and adolescents with obesity. The association between skin lesions and the HOMA score indicates that skin manifestations are a marker of insulin resistance. To prevent secondary diseases and improve QoL, thorough skin examinations and interdisciplinary cooperation are necessary.

Background: Mortality and morbidity in people with Type 1 diabetes (T1D) is mainly caused by cardiovascular disease (CVD). Early treatment of cardiovascular risk factors (CVRFs) is of great importance., Objective: To analyze the prevalence of LDL-hypercholesterolemia and other CVRFs in youth with T1D., Methods: Clinical and laboratory parameters, and vascular thickness measurement were obtained in youth with T1D (age 6-18 years, T1D duration >1 year) attending a diabetes clinic. LDL-hypercholesterolemia, microalbuminuria and arterial hypertension were defined as CVRFs., Results: A total of 333 youth (48% girls; age: 13.3 years [10.3-15.5], median [interquartile range]) participated in the study. The T1D duration was 5.9 years [3.5-9.4] with HbA1c of 7.4% [6.8-8.0]. Intima media thickness (N=223) was 538.0 µm [470.0-618.0]). LDL-hypercholesterolemia was present in 30 participants (9%; 18 girls; age: 14.3 years [11.2-15.7]). None of the participants had persistent microalbuminuria, although 59 (18.3%) had elevated albumin excretion in a random urine specimen. LDL-hypercholesterolemia was associated with increased blood pressure (p<0.05), insulin requirement (p<0.05), HbA1c (p<0.05), triglyceride (p<0.001) and total cholesterol (p<0.001), and a family history of premature CVD (p<0.001), but negatively correlated with HDL cholesterol levels (p<0.05). Sex, pubertal status, duration of diabetes, type of therapy, and physical activity did not differ between participants with and without LDL- hypercholesterolemia. Arterial hypertension was present in 11 participants (3.3%; 4 girls; age: 14.1 years [11.1-16.1])., Conclusion: LDL-hypercholesterolemia affected 9% of youth with T1D in this cohort and was associated with other CVRFs. A holistic therapeutic concept for these young people is essential., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: This study aimed to evaluate the impact of the COVID-19 pandemic on the nutritional patterns, eating behavior, dietary content, and health-related quality of life (HrQoL) of adolescents with preexisting obesity., Methods: Anthropometric and metabolic parameters were measured, and validated questionnaires on eating habits, nutritional content, and HrQoL were administered to 264 adolescents with obesity during the COVID-19 pandemic (June 2020-June 2022) and 265 adolescents with obesity before the pandemic (from June 2017 to June 2019)., Results: Both study cohorts were comparable in age and sex distribution. Significant differences were found between the COVID-19 and pre-COVID-19 cohorts in HOMA-index (3.8 (interquartile range [IQR])): 3.3; 4.1) vs. 3.2 (IQR: 2.8; 3.5, p < 0.001), total cholesterol (208.8 mg/dL (IQR: 189.9; 214.5) vs. 198.5 mg/dL (IQR: 189.5; 207.4), p < 0.001), and GPT (93.4 (IQR 88.7; 96.5) vs. 72.8 U/L (IQR 68.9; 75.7), p < 0.001). The COVID-19 cohort reported significantly higher consumption of obesity-promoting food components, such as soft drinks, meat, sausages, fast food and delivery food, chocolate, and sweets. There was also a significant decrease in cognitive hunger control ( p = 0.002) and an increase in distractibility potential ( p = 0.001) while eating. HrQoL was significantly lower in the COVID-19 cohort ( p = 0.001)., Conclusions: This study reveals the adverse associations of exposure to the public health measures during the COVID-19 pandemic with nutrition, dietary content, and HrQoL in adolescents with preexisting obesity. These findings underscore the importance of tailored preventive and treatment strategies for addressing the specific challenges of disruptive events such as pandemics, especially in population-based context.

As the most visible and vulnerable organ of the human organism, the skin can provide an impression of its state of health. Rare forms of diabetes and endocrinopathies are often diagnosed late or primarily misinterpreted due to their rarity. Skin peculiarities associated with these rare diseases may be indicative of the underlying endocrinopathy or form of diabetes. At the same time, rare skin changes in diabetes or endocrinopathies can also be a major challenge for dermatologists, diabetologists and endocrinologists in optimal patient and therapy management. Active collaboration between these different specialist groups can therefore lead to increased patient safety, better therapeutic success and more targeted diagnostics.

Aim: To assess effects of the SARS-CoV2 pandemic on metabolic control in youth with type 1 diabetes (T1D) in Germany in a population-based analysis., Methods: Data from 33,372 pediatric T1D patients from the Diabetes Prospective Follow-up (DPV) registry, with face-to-face visits or telemedicine contacts in the years 2019-2021, were available. Datasets from eight time periods between March 15, 2020, and December 31, 2021, according to SARS-CoV2 incidence waves, were compared to those from five control time periods. Parameters of metabolic control were assessed with adjustment for sex, age, diabetes duration, and repeated measurements. Laboratory-measured HbA1c values and those estimated from CGM were aggregated into a combined glucose indicator (CGI)., Results: There was no clinically relevant difference in metabolic control between pandemic and control time periods with adjusted CGI values ranging from 7.61% [7.60-7.63] (mean [95% confidence interval (CI)]) in the third quarter of 2019 to 7.83% [7.82-7.85] in the time period from January 1 to March 15 2020, in the other control periods, and during the pandemic, CGI values lay between these values. BMI-SDS rose during the pandemic from 0.29 [0.28-0.30] (mean [95% CI]) in the third quarter of 2019 to 0.40 [0.39-0.41] during the fourth wave. Adjusted insulin dose rose during the pandemic. Event rates for hypoglycemic coma and diabetic ketoacidosis remained unchanged., Conclusions: We found no clinically relevant change of glycemic control or incidence of acute diabetes complications during the pandemic. The observed BMI increase may represent an important health risk for youth with T1D., (© 2023. The Author(s).)

Objective: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally., Research Design and Methods: We analyzed data on 17,280 cases of T1D diagnosed during 2018-2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models., Results: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1-12.2) in 2018 to 21.7 (20.6-22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2-14.0) in 2018 to 26.7 (25.7-27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5-12.9) to 24.7 (24.0-25.5) for adolescents ages 12-18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018-2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic., Conclusions: The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent., (© 2022 by the American Diabetes Association.)

Aim: To obtain additional information on the incremental differences between using a sensor-augmented pump (SAP) without automated insulin delivery (AID), using it with predictive low-glucose management (PLGM) or as hybrid closed loop (HCL), in preschool and school children., Methods: We conducted a monocentric, randomized, controlled, two-phase crossover study in 38 children aged 2-6 and 7-14 years. The primary endpoint was the percentage of time in range (TIR) of 70-180 mg/dl. Other continuous glucose sensor metrics, HbA1c, patient-related outcomes (DISABKIDS questionnaire, Fear of Hypoglycaemia Survey) and safety events were also assessed. Results from 2 weeks of SAP, 8 weeks of PLGM and 8 weeks of HCL were compared using a paired t-test or Wilcoxon signed-rank test., Results: Overall, we found a high rate of TIR target (>70%) achievement with HCL in preschool (88%) and school children (50%), with average times in Auto Mode of 93% and 87%, respectively. Preschool children achieved a mean TIR of 73% ± 6% (+8% vs. SAP, +6% vs. PLGM) and school children 69% ± 8% (+15% vs. SAP and + 14% vs. PLGM). Overall, HbA1c improved from 7.4% ± 0.9% to 6.9% ± 0.5% (P = .0002). Diabetes burden and worries and fear of hypoglycaemia remained at low levels, without significant changes versus PLGM. No events of severe hypoglycaemia or diabetic ketoacidosis occurred., Conclusions: Preschool children profit from AID at least as much as those aged 7 years and older. To ensure safe use and prescribing modalities, regulatory approval is also required for young children., (© 2022 John Wiley & Sons Ltd.)

Objectives: To investigate if digital approaches can ameliorate the known consequences of social-distancing restrictions in the context of the global COVID-19 pandemic for adolescent participants originally registered for a face-to-face outpatient weight regulation program and whether video-based multiprofessional outpatient obesity therapy is successful for a group of adolescents with preexisting obesity., Methods: The certified KiCK outpatient training program for children and adolescents with overweight and obesity was remodeled as a consequence of the lockdown traditional face-to-face program to a completely digital and video-based format on short notice. The virtual approach was compared with the results of the conventional program regarding metabolic parameters, body mass index standard deviation score (BMI SDS), well-being, and physical fitness., Results: Sixty-nine of 77 enrolled participants for KiCK (age 8 to 17 years, BMI z score >2.0) were able and willing to participate virtually. After the first lockdown significant improvements of BMI SDS (mean 0.18; p=0.02), homeostasis model assessment (HOMA) index (mean 1.4; p=0.016), triglycerides (mean 0.18 mmol/dL; p=0.021), 6 minute-walk-test (mean 97.0 m; p=0.030, and well-being according to the World Health Organization 5 (WHO-5) questionnaire (mean 2.5; p=0.002) were found after the virtual intervention, which was comparable to the results observed previously in matched pairs data from the program during the pre-COVID period. After the end of the second lockdown weight SDS, BMI SDS, HOMA INDEX, and cholesterol were also measured reduced compared to baseline parameters measured before program initiation. Walking distance in the 6 MWT and improvement in general well-being in the WHO-5 questionnaire also persisted., Conclusions: These results indicate good acceptance and efficacy of the video-intervention for youth with overweight and obesity during the lockdown, supporting the use of virtual modules in future programs after the pandemic., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To assess if metabolic control worsened during the SARS-CoV2 lockdown in spring 2020 in youth with type 1 diabetes (T1D) in Germany., Methods: Data from 19,729 pediatric T1D patients from the diabetes prospective follow-up (DPV) registry were available. Data sets from four time-periods between January 1 and June 30, 2020, were compared with data from the whole year 2019 in the same patient; differences were adjusted for seasonality, increasing age, and longer diabetes duration. HbA1c values from laboratory measurements and estimates derived from continuous glucose monitoring (CGM) were aggregated into a combined glucose indicator (CGI), expressed in analogy to HbA1c., Results: Based on regression models adjusted for differences of sex, age, diabetes duration, and migratory background between the four time-periods, CGI values in 2020 were slightly higher than in 2019, for example, by 0.044% (0.042-0.046) (median [95% CI]) in the second lockdown month, time-period 3. Insulin dose and BMI-SDS were also marginally higher. In 2020, there were fewer hospitalizations (e.g., incidence risk ratio in time-period 3 compared with 2019: 0.52 [95% CI: 0.46-0.58]). In a subgroup of patients reporting CGM data in both years, metrics in 2020 improved: time in target increased, and mean sensor glucose fell, for example, by 2.8% (2.7-2.9), and by 4.4 mg/dl (4.3-4.6) in time-period 3., Conclusion: Before, during, and after the lockdown in spring 2020, metabolic control in youth with T1D in Germany did not differ significantly from the preceding year. Further effects of the ongoing pandemic on pediatric T1D patients need to be evaluated., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Objectives: With this study, our aim was to quantify the relative risk (RR) of diabetic ketoacidosis at diagnosis of type 1 diabetes during the year 2020 and to assess whether it was associated with the regional incidence of coronavirus disease 2019 (COVID-19) cases and deaths., Methods: Multicenter cohort study based on data from the German Diabetes Prospective Follow-up Registry. The monthly RR for ketoacidosis in 2020 was estimated from observed and expected rates in 3238 children with new-onset type 1 diabetes. Expected rates were derived from data from 2000 to 2019 by using a multivariable logistic trend regression model. The association between the regional incidence of COVID-19 and the rate of ketoacidosis was investigated by applying a log-binomial mixed-effects model to weekly data with Germany divided into 5 regions., Results: The observed versus expected frequency of diabetic ketoacidosis was significantly higher from April to September and in December (mean adjusted RRs, 1.48-1.96). During the first half of 2020, each increase in the regional weekly incidence of COVID-19 by 50 cases or 1 death per 100 000 population was associated with an increase in the RR of diabetic ketoacidosis of 1.40 (95% confidence interval, 1.10-1.77; P = .006) and 1.23 (1.14-1.32; P < .001), respectively. This association was no longer evident during the second half of 2020., Conclusions: These findings suggest that the local severity of the pandemic rather than health policy measures appear to be the main reason for the increase in diabetic ketoacidosis and thus the delayed use of health care during the pandemic., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Prof Raile is an advisory board member of Lilly Diabetes and Abbott Diabetes Care and reports paid talks for Sanofi, Dexcom Continuous Glucose Monitoring, Novo Nordisk, and Springer Healthcare outside the submitted work. Dr Mönkemöller received educational fees from Medtronic outside the submitted work; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To study the impact of the quality of therapeutic control on fertility and on the prevalence of testicular adrenal rest tumours (TART) in young males with congenital adrenal hyperplasia (CAH)., Design: Combined cross-sectional and retrospective clinical study., Methods: Twenty-nine patients and age-matched controls underwent clinical investigation, including semen analysis, testicular and adrenal ultrasound imaging, and serum and hair steroid analysis. The quality of therapeutic control was categorized as 'poor', 'moderate' or 'medium'. Evaluation of current control was based on concentrations of 17-hydroxy-progesterone and androstenedione in serum and 3 cm hair; previous control was categorized based on serum 17-hydroxy-progesterone concentrations during childhood and puberty, anthropometric and puberty data, bone age data and adrenal sizes., Results: Semen quality was similar in males with CAH and controls (P = 0.066), however patients with 'poor' past control and large TART, or with 'poor' current CAH control had low sperm counts. Follicle-stimulating hormone was decreased, if current CAH control was 'poor' (1.8 ± 0.9 U/L; 'good': 3.9 ± 2.2 U/L); P = 0.015); luteinizing hormone was decreased if it was 'poor' (1.8 ± 0.9 U/L; P = 0.041) or 'moderate' (1.9 ± 0.6 U/L; 'good': 3.0 ± 1.3 U/L; P = 0.025). None of the males with 'good' past CAH control, 50% of those with 'moderate' past control and 80% with 'poor past control had bilateral TART. The prevalence of TART in males with severe (class null or A) CYP21A2 mutations was 53% and 25% and 0% in those with milder class B and C mutations, respectively., Conclusions: TART development is favoured by inadequate long-term hormonal control in CAH. Reduced semen quality may be associated with large TART. Gonadotropin suppression by adrenal androgen excess during the latest spermatogenic cycle may contribute to impairment of spermatogenesis.

Background: Wolfram Syndrome is a very rare genetic disease causing diabetes mellitus, blindness, deafness, diabetes insipidus, and progressive brainstem degeneration. Neurologic symptoms of affected patients include ataxia, sleep apnea, loss of bladder control, dysphagia, loss of taste, and accompanying psychiatric symptoms as a sign of progressive neurodegeneration. Its genetic cause is mainly biallelic mutations of the Wolframin endoplasmatic reticulum transmembrane glycoprotein gene Wfs1. These result in increased ER stress, which in turn induces apoptosis and leads to the depletion of the corresponding cells and a loss of their physiological functions. Though diabetes mellitus is mostly treated by insulin, there is still no proven cure for the disease in general. It leads to premature death in affected individuals-usually within the 4th decade of live., Current Research and Treatment Trials: Clinical studies are currently being conducted at various locations worldwide to test a therapy for the disease using various approaches., Potentail of Virtual Netowrking: As rare diseases in general represent a major challenge for individual clinicians and researchers due to the rarity of diagnosis, the lack of evidence and of value of existing research, international cooperation, coordination and networking leading to an alignment of different stakeholders is necessary to support patients and increase knowledge about these diseases, like wolfram syndrome., Conclusion: ENDO-ERN and EURRECA are two EU-funded networks that aim to promote knowledge sharing, education and research on rare endocrine diseases.

Background: Alström syndrome (ALMS) is a monogenic ultra-rare disorder with a prevalence of one per million inhabitants caused by pathogenic variants of ALMS1 gene. ALMS1 is located on chromosome 2p13, spans 23 exons and encodes a predicted 461.2-kDa protein of 4169 amino acids. The infantile cone-rod dystrophy with nystagmus and severe visual impairment is the earliest and most consistent clinical manifestation of ALMS. In addition, infantile transient cardiomyopathy, early childhood obesity with hyperphagia, deafness, insulin resistance (IR), type 2 diabetes mellitus (T2DM), systemic fibrosis and progressive renal or liver dysfunction are common findings. ALMS1 encodes a large ubiquitously expressed protein that is associated with the centrosome and the basal body of primary cilium., Current Research: The localisation of ALMS1 to the ciliary basal body suggests its contribution to ciliogenesis and/or normal ciliary function, or centriolar stability. ALMS1 regulate glucose transport through the actin cytoskeleton, which plays an important role in insulin-stimulated GLUT4 transport. Both extreme IR and β-cell failure are the two determinant factors responsible for the development of glucose metabolism alterations in ALMS., Treatment: Currently, there is no known cure for ALMS other than managing the underlying systemic diseases. When possible, individuals with ALMS and families should be referred to a centre of expertise and followed by a multidisciplinary team. Lifestyle modification, aerobic exercise and dietary induced weight loss are highly recommended as primary treatment for ALMS patients with T2DM and obesity., Conclusion: Managing a rare disease requires not only medical care but also a support network including patient associations.

Undescended testes are a very common congenital problem of the urogenital tract. Altered spermatogenesis and fertility as well as an elevated risk for oncologic degeneration are known facts associated with testicular malposition. There is broad international consensus among the various disciplines that the treatment of undescended testes should be completed by the age of 12 months. Following the guideline of the German Working Group of Scientific Medical Societies (AWMF), hormonal treatment should be offered to patients with bilateral undescended testicles. This article reviews the literature and disputes the reasoning of the recommendation to treat undescended testes hormonally., Competing Interests: Der Autor gibt an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

It has been known for more than 20 years that early treatment of maldescended testicles can have a positive effect on fertility and a negative effect on the development of tumors. In certain circumstances, hormone therapy is still recommended in German-speaking countries. However, its benefit is still controversially discussed. Therapy is usually initiated by the pediatrician, who is usually the first to detect undescended testicles. Since therapy may involve early hormone therapy as well as surgery, acceptance among pediatricians and also the parents may be reduced. The question also arises as to how far the implementation is practicable. In patients with nonpalpable testis, there are many controversies concerning the value of ultrasound investigations. In the following two case studies, the treatment decisions for undescended testes in infancy are exemplified. Furthermore, the available evidence from the literature and guidelines is presented to provide assistance for daily routine care and to critically discuss potential fields of application and limitations of existing guidelines.

The association between smell impairment and chronic diseases has been reported in some studies in adults. Such information is not available for chronic diseases in children. The aim of this study was to examine olfactory function of children with chronic diseases such as diabetes mellitus type 1, hypothyroidism, and bronchial asthma in combination with allergic rhinitis in comparison to healthy controls. The data were obtained from n = 205 participants (104 boys, 101 girls) between the age of 6 and 17 years. Seventy-eight of the participants were healthy controls, n = 43 had diabetes mellitus type 1, n = 50 suffer from allergic rhinitis or bronchial asthma, and 34 presented a reduced function of their thyroid in medical history. All participants underwent olfactory testing including olfactory threshold using "Sniffin' Sticks" and odor identification using the "U-Sniff" test. In addition, a depression inventory and cognitive testing using the Ravens Progressive Matrices was performed. No significant difference in olfactory function was observed for any of the chronic diseases in children in comparison to healthy controls. Further analysis showed a trend in significance for a subpopulation of children with bronchial asthma and comorbidities performed worse on the olfactory threshold test compared to patients with bronchial asthma without comorbidities. Pediatric patients suffering from chronic diseases scored higher on the depression inventory compared to healthy controls.Conclusion: In conclusion, this study demonstrates that the influence of chronic diseases (bronchial asthma, diabetes mellitus type 1 and hypothyroidism) on olfactory function in childhood, if any, seems to be insignificant. This is partly in contrast to adult patients. Further research should be conducted in a subgroup of patients with bronchial asthma, allergic rhinitis, and atopic dermatitis or other comorbidities to better understand the association of allergic diathesis and olfactory function and the putative pathogenesis of olfactory dysfunction. What is known: • The association between smell impairment and chronic diseases has been reported in some studies in adults. • Such information is not available for chronic diseases in children. What is new: • The influence of chronic diseases (bronchial asthma, diabetes mellitus type 1, and hypothyroidism) on olfactory function in childhood, if any, seems to be insignificant. • In patients with bronchial asthma and allergic rhinitis, only a subgroup of patients with additional comorbidity (atopic dermatitis) showed a tendency to a reduced sense of smell.

Background: Triple A syndrome (MIM #231550) is associated with mutations in the AAAS gene. However, about 30% of patients with triple A syndrome symptoms but an unresolved diagnosis do not harbour mutations in AAAS ., Objective: Search for novel genetic defects in families with a triple A-like phenotype in whom AAAS mutations are not detected., Methods: Genome-wide linkage analysis, whole-exome sequencing and functional analyses were used to discover and verify a novel genetic defect in two families with achalasia, alacrima, myopathy and further symptoms. Effect and pathogenicity of the mutation were verified by cell biological studies., Results: We identified a homozygous splice mutation in TRAPPC11 (c.1893+3A>G, [NM&#95;021942.5], g.4:184,607,904A>G [hg19]) in four patients from two unrelated families leading to incomplete exon skipping and reduction in full-length mRNA levels. TRAPPC11 encodes for trafficking protein particle complex subunit 11 (TRAPPC11), a protein of the transport protein particle (TRAPP) complex. Western blot analysis revealed a dramatic decrease in full-length TRAPPC11 protein levels and hypoglycosylation of LAMP1. Trafficking experiments in patient fibroblasts revealed a delayed arrival of marker proteins in the Golgi and a delay in their release from the Golgi to the plasma membrane. Mutations in TRAPPC11 have previously been described to cause limb-girdle muscular dystrophy type 2S (MIM #615356). Indeed, muscle histology of our patients also revealed mild dystrophic changes. Immunohistochemically, β-sarcoglycan was absent from focal patches., Conclusions: The identified novel TRAPPC11 mutation represents an expansion of the myopathy phenotype described before and is characterised particularly by achalasia, alacrima, neurological and muscular phenotypes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)