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Background/Objectives: Vitamin B12 (B12) is essential for the provision of methyl groups for numerous essential pathways. Infant B12 deficiency (B12D) can lead to severe, even irreversible neurological abnormalities. Maternal B12 status in pregnancy and during the breastfeeding period correlates significantly with the child’s B12 status. B12D is a target disease in some newborn screening (NBS) programs. This study investigates whether infants that were clinically symptomatic and diagnosed with B12D in their first year of life could be retrospectively detected by the Austrian NBS algorithm. Methods: Data from infants with clinically diagnosed B12D in their first year of life between 2012 and 2022 were retrospectively collected in Austria (B12-related NBS implemented in 2018) and Switzerland (B12-related NBS not implemented). NBS data were retrospectively analysed, and clinical information was collected by a survey. Correlations between clinical symptoms, NBS data, biochemical parameters at diagnosis, maternal medical history and B12 status were analysed. Results: Four/forty-eight cases were retrospectively detected by the first-tier NBS parameters. From two children material for second-tier testing was available and B12D was confirmed by elevated total homocysteine (tHcy), resulting in a detection rate between 4.3 and 9.3%. The numbers of neurological and haematological symptoms correlated with low B12 and elevated levels of tHcy and methylmalonic acid. Although the detection rate of symptomatic B12D by NBS was low, fewer infants with symptomatic B12D were observed in the period after implementation of B12-related NBS (Austria). A history of B12D-relevant maternal disease such as pernicious anaemia was reported in 12 cases. Conclusions: B12D causes severe clinical symptoms in infants. NBS has a very limited retrospective detection rate of infants with severe B12D but seems to correlate with a reduction in cases due to not yet precisely quantified mechanisms. The workup triggered by NBS recalls is costly and often challenging for families. Maternal B12D increases the risk of infant B12D but also of other pregnancy-related health risks. To increase the efficacy of the prevention of infant B12D, to promote a healthy pregnancy and breastfeeding period, and to reduce the frequency of NBS recalls, pregnant women should be screened for B12D to be counselled and treated.

Congenital primary hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) are targeted by the German and Austrian newborn screening. For both diseases, there are registries for quality improvement, based on standardized observational data from long-term patient follow-up, under the auspices of the DGKED study group. By September 2021, the CH registry HypoDOK includes datasets from 23,348 visits of 1,840 patients, and the CAH registry contains datasets from 36,237 visits of 1,976 patients. Here, we report on the recruitment process, patient characteristics, and research contributions from the registries, and underline that the registries are an important tool to improve patient care and outcomes. Registries for rare conditions should thus be considered as an important public health measure and they should be adequately institutionalized and funded.

Background 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 studies have been undertaken in Germany. Aims Description of the phenotype, evaluation of the diagnostics and genotype-phenotype correlation Patients and methodology Retrospective analysis of the data of 134 patients (age range 0.1–18.6 years) in a multicentre study covering 10 paediatric endocrinology centres in Bavaria and Baden-Württemberg. The data was gathered on site from the medical records. Two hundred and thirty-three alleles with a mutation of the CYP21A2 gene were identified in 126 patients. A genotype-phenotype correlation of the mutation findings was undertaken (C1, severe/mild; C2, mild/mild). Individuals with a heterozygous mutation of the CYP21A2 were also included (C3). The data was collected with the approval of the ethics committee of the University Hospital of Erlangen during the period of 2014 and 2015. Results (MW ± SD) One hundred and seventeen out of 134 patients (115 f, 29 m) were symptomatic. The chronological age (CA) at diagnosis was 7.1 ± 4.4 years. The most frequent symptom (73.5%) was premature pubarche. The height-SDS on diagnosis was 0.8 ± 1.3 and the BMI-SDS was 0.8 ± 1.2. Bone age (BA) was ascertained in 82.9% of the symptomatic patients. The difference between BA and CA was 1.9 ± 1.4 years. Basal 17OHP concentrations were 14.5 ± 19.1 ng/ml (18 patients < 2 ng/ml). In total, 58.1% mild and 34.7% severe mutations were found. The most common mutation was p.Val281Leu (39.1%); 65.8% of the patients could be allocated to group C1. No phenotypical differences were found between the 3 mutation groups. The 17OHP levels (basal and after ACTH) in the standard ACTH stimulation test were highest in group C1 and also significantly higher in group C2 as in C3, the ACTH-stimulated cortisol levels (ng/ml) were significantly lower in groups C1 (192.1 ± 62.5) and C2 (218 ± 50) than in C3 (297.3 ± 98.7). Conclusion Most of the patients have symptoms of mild androgenisation. Male patients are underdiagnosed. Diagnostics are not standardised. Differences between the types of mutations are found in the hormone concentrations but not in phenotype. We speculate that further, as yet not clearly defined, factors are responsible for the development of the respective phenotypes.

OBJECTIVE:--The aim of this study was to establish whether type 1 diabetes has a long-term effect on bone development in children and adolescents. RESEARCH DESIGN AND METHODS--Bone characteristics and muscle cross-sectional area (CSA) were analyzed cross-sectionally in 41 (19 female and 22 male) patients and were reevaluated after 5.56 ± 0.4 years using peripheral quantitative computed tomography (pQCT). We hypothesize that bone size and muscle mass normalize with age. RESULTS:--At the first evaluation, mean ± SD age was 9.87 ± 2.3 years and disease duration was 4.31 ± 2.9 years. Height was -0.36 ± 1.9 SD, and BMI was 0.39 ± 0.9 SD. Parameters of bone size were low in the whole patient group (corrected for patient's height). At reevaluation, age was 15.44 ± 2.3 years, and patients had a mean height of -0.12 ± 0.8 SD. BMI SD had increased to 0.57 ± 1.1. Total and cortical CSA had normalized. Those patients with an increase in total CSA had a significant younger age at disease manifestation and a younger age at initial pQCT measurement. Bone size was well adapted to muscle mass expressed as the ratio of bone mineral content per muscle mass, and a close correlation was shown between the increase in bone size and in muscle CSA (r = 0.46, P = 0.03). CONCLUSIONS:--Patients with manifestation of type 1 diabetes at an early age had transient impaired bone development. Within the follow-up period, the greatest increase in bone size was found in these patients. In adolescence, all patients had a normal bone size and appropriate adaptation of bone on muscle.

Close adherence to the recommended treatment regimen is important for the success of recombinant human growth hormone therapy, although nonadherence can be common. Ease of use and safety during use/storage are among several important factors in the design of a growth hormone injection device intended for long-term use. This study was performed to validate the usability and assess the ease of use of a new pen device (SurePal™) that has been developed to support daily administration of the recombinant human growth hormone product, Omnitrope® (somatropin). The primary objectives of the study were to assess if study participants, representing intended users of the pen in clinical practice, were able to perform an injection procedure into an injection pad effectively and safely and disassemble the pen without receiving a needlestick injury. A total of 106 participants (61 adults and 45 children/adolescents) were enrolled at two study centers (one in the US, one in Germany). Results for both primary usability tasks met the predefined acceptance criteria, with >85% of participants successfully performing each task. All of the other tasks/handling steps assessed were also successfully performed by most participants, with high success rates reflected in the high proportion of participants who classified each task as \"very easy\" or \"easy\". After a second use of the device, 87%-97% of participants rated it as \"very easy\" or \"easy\" to use. In summary, the new pen device is safe and easy to use for both adults and children, and will help to support effective, long-term daily administration of the recombinant human growth hormone product, Omnitrope®.

In the state of insulin deficiency, the growth hormone—insulin-like growth factor-I (GH–IGF-I) axis is altered due to hepatic GH resistance, which leads to GH hypersecretion and low circulating IGF-I concentration. On the other hand, both growth hormone deficiency (GHD) and GH excess have significant influence on carbohydrate metabolism. These complex interactions are challenging in diagnosing GHD in subjects with type 1 diabetes mellitus (T1DM) and in treating subjects with T1DM with GH. So far, there is only limited clinical experience in GH treatment in patients with T1DM, but recently first reports on metabolic safety and efficacy of GH treatment in subjects with T1DM have been published.

Abstract Context Treatment of children with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is challenging. Linear growth and adult height are compromised according to recent publications. However, most of these data were obtained in the era before CAH newborn screening. Design Body height of patients with classical CAH diagnosed before and after the establishment of newborn screening were analyzed retrospectively. Patients and Methods We identified 600 patients with classical CAH (227 male) with data on near-adult height (NAH), target height (TH), and information on newborn screening from the electronic German CAH registry (German Society for Paediatric Endocrinology and Diabetology). Newborn screening was performed in 101 (16.8%) patients. All patients received hydrocortisone with or without fludrocortisone. To assess the effects of newborn screening, a linear regression model adjusted/stratified for sex and phenotype was used (SAS 9.4). Results TH corrected NAH (mean; 95% confidence interval) was closer to 0 in patients with CAH and newborn screening [−0.25 standard deviation score (SDS); −0.44 to −0.06] than in patients without newborn screening (−0.44 SDS; −0.52 to −0.36) (P = .069). Screening had no effect on NAH in female patients. In male patients, NAH was significantly better (P = .033) with screening than without screening. After stratifying for CAH phenotype, screening did not affect the NAH of patients with salt-wasting CAH. Patients with simple-virilizing CAH had a significantly better cNAH (P = .034) with screening (0.15 SDS; −0.28-0.59) than without screening (−0.35 SDS; −0.52 to −0.18). Conclusions Our data suggest that newborn screening might be associated with improved NAH in male CAH patients and in patients with simple-virilizing CAH.

No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency. To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency. Observational, retrospective, longitudinal analysis. A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison disease (AD) were analysed. PRC, electrolytes, blood pressure (BP), and anthropometric parameters were used to predict their utility in optimizing MC replacement dose. PRC was low, normal, or high in 19%, 36%, and 44% of patients, respectively, with wide variability in MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC. The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration.

Purpose To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults. Methods A structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity. Results Of the 31 (67%) centres from 15 countries that completed the survey, 30 (97%) screened for hypertension by measuring blood pressure, 30 (97%) screened for obesity, 26 (84%) screened for abnormal glucose homoeostasis mainly by using Hb1Ac (73%), 25 (81%) screened for osteoporosis mainly by DXA (92%), 20 (65%) screened for hyperlipidaemia and 6 (19%) screened for additional CV disease. Of the 31 centres, 13 provided further information on the six co-morbidities in 244 patients with a median age of 33 yrs (range 19, 94). Of these, 126 (52%) were females and 174 (71%) received fludrocortisone in addition to glucocorticoids. Of the 244 adults, 73 (30%) were treated for at least one comorbidity and 15 (21%) for more than 2 co-morbidities. Of 73, the patients who were treated for osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity were 43 (59%), 17 (23%), 16 (22%), 10 (14%), 8 (11), 3 (4%) respectively. Conclusion Cardiometabolic and bone morbidities are not uncommon in adults with CAH. There is a need to standardise the screening for these morbidities from early adulthood and to explore optimal therapy through routine collection of standardised data.