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.

Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable.

Classic galactosemia is a rare metabolic disorder resulting from galactose‐1‐phosphate uridylyltransferase deficiency, which disrupts normal galactose metabolism, leading to toxic accumulation of galactose‐1‐phosphate and galactitol. Despite early dietary intervention, patients remain at risk for long‐term neurological impairments, including cognitive deficits, motor speech disorders, and psychiatric conditions. The mechanisms driving these persistent abnormalities remain unclear. This study investigated brain metabolic and structural alterations in adults with classic galactosemia using advanced multiparametric MRI. Six patients (3 males, 3 females; mean age 34.0 ± 7.3 years) adhering to lifelong galactose‐restricted diets and six age‐ and sex‐matched controls underwent 3T and 7T MRI, including T1‐weighted imaging, pseudo‐continuous arterial spin labeling, and high‐resolution MR spectroscopic imaging. Patients exhibited significantly lower myo‐inositol (mIns) concentrations in cerebellum ( p = 0.007), putamen ( p = 0.023), and cerebral white matter ( p = 0.001), reflecting a chronic mIns deficiency despite dietary management. Structural analyses revealed reduced volumes of white matter ( p < 0.001), bilateral putamen ( p < 0.038), and left thalamus ( p = 0.044); alongside increased cortical thickness and reduced cortical surface area, indicating abnormal cortical maturation, particularly in regions associated with motor and cognitive processing. Additionally, cerebral blood flow was elevated in emotion‐processing regions, including bilateral amygdala ( p < 0.022) and thalamus ( p < 0.038). These preliminary findings highlight persistent neurological alterations in classic galactosemia despite dietary management and suggest that chronic mIns deficiency may contribute to the pathophysiology. They underscore the need for larger, longitudinal studies to confirm these results, investigate potential correlations with clinical severity and biochemical markers, and explore therapeutic strategies aimed at modulating mIns metabolism.

In the last decade, health-related quality of life (HrQoL) has become an increasingly important outcome parameter in children and adolescents with chronic health conditions; among them are pediatric patients with inborn metabolic diseases (IMDs). Hence, knowledge on this topic is increasing, but findings on non-medical influences on the HrQoL of IMD patients are still scarce. In the present study, we retrospectively evaluated the self-reported generic HrQoL of a cohort of pediatric patients (ages 7 to 17 years) with diverse IMDs (n = 204) and explored associations between HrQoL and psychosocial and medical characteristics of the patients. We aimed to identify risk factors for impaired HrQoL to improve and tailor support for the patients and economize resources. Generic HrQoL was assessed with the KINDL-R questionnaire. We compared the HrQoL scores to published German normative data and analyzed the impact of demographic variables and intellectual and psychosocial functioning on the HrQoL. Moreover, we examined the influence of the diagnostic category and the health impairment (as judged by the physicians) on our patients’ HrQoL. Overall, the HrQoL of the adolescent patients was comparable to the HrQoL of the norm group. Disorders of intellectual development, impaired psychosocial functioning, and a severe health impairment were associated with lower HrQoL scores.Conclusion: We recommend evaluating these factors in children and adolescents with IMDs to identify patients at risk for impaired HrQoL. What is Known:• Studies on HrQoL in pediatric patients with IMDs mainly focused on subgroups with specific diagnoses and found normal HrQoL in some of those subgroups.• In healthy children and adolescents as well as in pediatric patients with various chronic diseases, associations between psychosocial factors and HrQoL are well known. What is New:• Impaired psychosocial functioning, disorders of intellectual development, and a significant disease and/or treatment burden are risk factors for impaired HrQoL in pediatric patients with IMDs.• Evaluating these factors in children and adolescents with IMDs can help identify patients and families in need of enhanced psychological support.

Eltern chronisch kranker Kinder sind vielfältigen Belastungen ausgesetzt, was zu negativen Auswirkungen auf ihre eigene psychische Gesundheit führen kann. Ihr Zugang zu adäquaten Behandlungsangeboten ist aus unterschiedlichen Gründen wie beispielsweise knappen zeitlichen Ressourcen oft erschwert. Internetbasierte Psychotherapie, deren Wirksamkeit bereits gut belegt ist, hat das Potenzial, auch für diese Zielgruppe eine Alternative zu konventioneller Psychotherapie darzustellen. Im Rahmen einer Pilotstudie wurde ein Inter-ventionsprogramm für Eltern eines Kindes mit Mukoviszidose als manualisierte kognitiv-behaviorale Schreibtherapie konzipiert, auf einer passwortgeschützten Internetplattform implementiert und anschließend hinsichtlich Mach-barkeit und Akzeptanz evaluiert. Das Interventionsprogramm erwies sich als gut durchführbar und wurde von den Teilnehmern gut akzeptiert. Eine Weiterentwicklung des Beratungsprogramms für Eltern von Kindern mit anderen seltenen Erkrankungen wird derzeit erprobt. Demands for caregivers of children with chronic conditions can be extensive and may lead to adverse consequences for their own mental health. Due to various reasons, e. g. limited time resources, their access to mental health care services is often limited. Internet-based psychotherapy, whose effectiveness is already well documented, has the potential to provide an alternative to conventional psychotherapy for this target group. Within the framework of a pilot study an intervention program for caregivers of children with cystic fibrosis was designed as manualised cognitive-behavioral writing therapy, implemented on a secure internet-platform and then its feasibility and acceptance were evaluated. The usability of the intervention program could be demonstrated and so far, the intervention seems to be well accepted by the target group. An adaptation of the program for parents with children with other rare diseases, where the efficacy of the program can be further evaluated, is currently under way. ^* derzeit beschäftigt bei: Medizinische Universität Wien, Klinik für Kinder- und Jugendheilkunde