Risk Scores for Metabolic Dysfunction-Associated Fatty Liver Disease in Pediatric Obesity.

INTRODUCTION: Early noninvasive detection of incipient liver damage is crucial to prevent long-term adverse health outcomes. A variety of scores to assess liver status have been proposed, mostly for adult populations. Validation of noninvasive hepatic scores to identify children at risk of metabolic dysfunction-associated fatty liver disease (MAFLD) is a gap in research, particularly in youth with severe obesity considering pubertal stage and sex. METHODS: In a well-characterized pediatric population aged 9-19 years (n = 115), 19 published liver scores were analyzed. The area under the receiver operating characteristic curve (AUROC) for determination of MAFLD as assessed by magnetic resonance imaging was calculated. RESULTS: The pediatric indices PNFI, B-AST, and M-APRI and several scores developed in adults significantly differed in children with MAFLD compared to children without, while some established indices did not. Only nonalcoholic fatty liver disease liver fat score (NAFLD-LFS) and the model by Cao et al. [PLoS One. 2013;8(12):e82092] showed acceptable predictive accuracy (AUROC >0.8) independently of pubertal stage and sex. When stratifying for pubertal stage and sex, the GSG-Index was superior in pubertal girls, and NAFLD-LFS performed best in pubertal boys. CONCLUSION: NAFLD-LFS and the model by Cao et al. [PLoS One. 2013;8(12):e82092] were well suited to predict MAFLD in youth with severe obesity. In pubertal children, GSG-Index and NAFLD-LFS performed best in girls and boys, respectively.

Plasma Myostatin Increases with Age in Male Youth and Negatively Correlates with Vitamin D in Severe Pediatric Obesity.

Obesity already causes non-communicable diseases during childhood, but the mechanisms of disease development are insufficiently understood. Myokines such as myostatin and irisin are muscle-derived factors possibly involved in obesity-associated diseases. This explorative study aims to investigate whether myostatin and irisin are associated with metabolic parameters, including the vitamin D status in pediatric patients with severe obesity. Clinical, anthropometric and laboratory data from 108 patients with severe obesity (>97th percentile) aged between 9 and 19 years were assessed. Myostatin, its antagonist follistatin, and irisin, were measured from plasma by ELISA. Myostatin concentrations, particularly in males, positively correlated with age and pubertal stage, as well as metabolic parameters such as insulin resistance. Irisin concentrations correlated positively with HDL and negatively with LDL cholesterol values. For follistatin, the associations with age and pubertal stage were inverse. Strikingly, a negative correlation of myostatin with serum vitamin D levels was observed that remained significant after adjusting for age and pubertal stage. In conclusion, there is an independent association of low vitamin D and elevated myostatin levels. Further research may focus on investigating means to prevent increased myostatin levels in interventional studies, which might open several venues to putative options to treat and prevent obesity-associated diseases.

Vascular access for lipid apheresis: a challenge in young children with homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (hoFH) is a rare genetic disorder leading to extremely increased LDL-cholesterol (LDL-C), resulting in high cardiovascular risk in early childhood. Lipid apheresis (LA) is an effective treatment and should be started as early as possible to prevent premature cardiovascular events. As peripheral punctures in children can be challenging due to small vessels and anxiety, this study aimed to evaluate feasibility and safety of central venous catheters (CVCs) as vascular access for LA in young children with hoFH. METHODS: Retrospective analysis (2016-2019) on four children with hoFH aged 3-5 years, performing weekly or biweekly LA with a CVC. RESULTS: LDL-C decreased by> 60%. In three children, the use of a permanent CVC for 698, 595, and 411 days, respectively, avoided difficult peripheral access, without the occurrence of occlusion or thrombosis. Unfortunately, one child had recurrent CVC-related infections and needed an arteriovenous fistula from the age of 5. Although the mean dwell time per catheter was 212 days, there were, as expected, severe side effects of early catheter infections with sepsis and accidental self-removal. Starting LA at an early age improved or stabilized carotid intima-media thickness (IMT) in three children. However, IMT did increase in one child caused by intolerance to peripheral punctures and LA interruption. CONCLUSIONS: Permanent CVCs are a viable temporary access choice for LA in young children with hoFH until peripheral venipuncture is practicable. The risk of CVC-related infections needs to be taken into account.

Rare skeletal disorders: a multidisciplinary postnatal approach to diagnosis and management.

Skeletal disorders are inherited disorders with significant skeletal involvement and most of them are rare or extremely rare. Based on the clinical, radiological and genetic phenotype, the group of skeletal disorder comprises more than 450 different and highly heterogeneous disorders. In skeletal disorders rapid and precise diagnoses are urgently needed for patient care and are based on the combination of clinical, radiological and genetic analysis. Novel genetic techniques have revolutionized diagnostics and have a huge impact on counseling of patients and families. Disease-specific long-term management in a multidisciplinary healthcare team in highly specialized centers is recommended to optimize care for these patients. Here we describe a multidisciplinary postnatal approach for the diagnosis and management of patients and families with rare skeletal disorders at the Vienna Bone and Growth Center. We discuss the value of a multidisciplinary diagnostic and management approach in the postnatal setting and provide a diagnostic flowchart for rare skeletal disorders.

A branched-chain amino acid-based metabolic score can predict liver fat in children and adolescents with severe obesity.

BACKGROUND: Eighty percent of adolescents with severe obesity suffer from non-alcoholic fatty liver disease (NAFLD). Non-invasive prediction models have been tested in adults, however, they performed poorly in paediatric populations. OBJECTIVE: This study aimed to investigate novel biomarkers for NAFLD and to develop a score that predicts liver fat in youth with severe obesity. METHODS: From a population with a BMI >97th percentile aged 9-19 years (n = 68), clinically thoroughly characterized including MRI-derived proton density fat fraction (MRI-PDFF), amino acids and acylcarnitines were measured by HPLC-MS. RESULTS: In children with NAFLD, higher levels of plasma branched-chain amino acids (BCAA) were determined. BCAAs correlated with MRI-PDFF (R = 0.46, p < .01). We identified a linear regression model adjusted for age, sex and pubertal stage consisting of BCAAs, ALT, GGT, ferritin and insulin that predicted MRI-PDFF (R = 0.75, p < .01). ROC analysis of this model revealed AUCs of 0.85, 0.85 and 0.92 for the detection of any, moderate and severe steatosis, respectively, thus markedly outperforming previously published scores. CONCLUSION: BCAAs could be an important link between obesity and other metabolic pathways. A BCAA-based metabolic score can predict steatosis grade in high-risk children and adolescents and may provide a feasible alternative to sophisticated methods like MRI or biopsy in the future.

Month-of-birth-effect in multiple sclerosis in Austria.

BACKGROUND: The month-of-birth-effect (MoBE) describes the finding that multiple sclerosis (MS) patients seem to have been born significantly more frequently in spring, with a rise in May, and significantly less often in autumn and winter with the fewest births in November. OBJECTIVES: To analyse if the MoBE can also be found in the Austrian MS population, and if so, whether the pattern is similar to the reported pattern in Canada, United Kingdom, and some Scandinavian countries. METHODS: The data of 7886 MS patients in Austria were compared to all live births in Austria from 1940 to 2010, that is, 7.256545 data entries of the Austrian birth registry and analysed in detail. RESULTS: Patterns observed in our MS cohort were not different from patterns in the general population, even when stratifying for gender. However, the noticeable and partly significant ups and downs over the examined years did not follow the distinct specific pattern with highest birth rates in spring and lowest birth rates in autumn that has been described previously for countries above the 49th latitude. CONCLUSION: After correcting for month-of-birth patterns in the general Austrian population, there is no evidence for the previously described MoBE in Austrian MS patients.