Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge. Methods: Whole-exome sequencing and targeted sequencing were used to detect the LEPR mutations. RNA analysis was performed to assess the effect of splice-site mutations. Results: In 2 unrelated girls with severe obesity, three novel LEPR mutations were detected. Longitudinal growth data show normal childhood growth, and in the older girl, a normal adult height despite hypogonadotropic hypogonadism and the lack of an obvious pubertal growth spurt. Bone age is remarkably advanced in the younger (prepubertal) girl, and bone mineral density (BMD) is high in both girls, which might be directly or indirectly related to leptin resistance. Conclusion: The spectrum of clinical features of LEPR deficiency may be expanded with increased BMD. Future observations in LEPR-deficient subjects should help further unravel the role of leptin in human bone biology

70 лет научно-исследовательскому институту охраны материнства и детства Минздрава Беларуси

НАУЧНО-ИССЛЕДОВАТЕЛЬСКИЕ ИНСТИТУТЫМАТЕРИ И РЕБЕНКА ОХРАНЫ ЗДОРОВЬЯ ЦЕНТРЫ /ИСТМЕДИЦИНСКИЕ ИНСТИТУТЫ /ИСТНАУЧНО-ИССЛЕДОВАТЕЛЬСКАЯ РАБОТАИСТОРИЯ МЕДИЦИН

Whole body composition analysis by the BodPod air-displacement plethysmography method in children with phenylketonuria shows a higher body fat percentage

BACKGROUND: Phenylketonuria (PKU) causes irreversible central nervous system damage unless a phenylalanine (PHE) restricted diet with amino acid supplementation is maintained. To prevent growth retardation, a protein/amino acid intake beyond the recommended dietary protein allowance is mandatory. However, data regarding disease and/or diet related changes in body composition are inconclusive and retarded growth and/or adiposity is still reported. The BodPod whole body air-displacement plethysmography method is a fast, safe and accurate technique to measure body composition. AIM: To gain more insight into the body composition of children with PKU. METHODS: Patients diagnosed with PKU born between 1991 and 2001 were included. Patients were identified by neonatal screening and treated in our centre. Body composition was measured using the BodPod system (Life Measurement Incorporation©). Blood PHE values determined every 1–3 months in the year preceding BodPod analysis were collected. Patients were matched for gender and age with data of healthy control subjects. Independent samples t tests, Mann–Whitney and linear regression were used for statistical analysis. RESULTS: The mean body fat percentage in patients with PKU (n = 20) was significantly higher compared to healthy controls (n = 20) (25.2% vs 18.4%; p = 0.002), especially in girls above 11 years of age (30.1% vs 21.5%; p = 0.027). Body fat percentage increased with rising body weight in patients with PKU only (R = 0.693, p = 0.001), but did not correlate with mean blood PHE level (R = 0.079, p = 0.740). CONCLUSION: Our data show a higher body fat percentage in patients with PKU, especially in girls above 11 years of age

PAPSS2 deficiency causes androgen excess via impaired DHEA sulfation-in vitro and in vivo studies in a family harboring two novel PAPSS2 mutations

Copyrigh

Birth weight in a large series of triplets

Background: Triplets are often born premature and with a low birth weight. Because the incidence of triplet births is rare, there are relatively few studies describing triplet birth weight characteristics. Earlier studies are often characterized by small sample sizes and lack information on important background variables such as zygosity. The objective of this study is to examine factors associated with birth weight in a large, population-based sample of triplets registered with the Netherlands Twin Register (NTR).Methods: In a sample of 1230 triplets from 410 families, the effects of assisted reproductive techniques, zygosity, birth order, gestational age, sex, maternal smoking and alcohol consumption during pregnancy on birth weight were assessed. The resemblance among triplets for birth weight was estimated as a function of zygosity. Birth weight discordance within families was studied by the pair-wise difference between triplets, expressed as a percentage of the birth weight of the heaviest child. We compare data from triplets registered with the NTR with data from population records, which include live births, stillbirths and children that have deceased within days after birth.Results: There was no effect of assisted reproductive techniques on triplet birth weight. At gestational age 24 to 40 weeks triplets gained on average 130 grams per week; boys weighed 110 grams more than girls and triplets of smoking mothers weighted 104 grams less than children of non-smoking mothers. Monozygotic triplets had lower birth weights than di- and trizygotic triplets and birth weight discordance was smaller in monozygotic triplets than in di- and trizygotic triplets. The correlation in birth weight among monozygotic and dizygotic triplets was 0.42 and 0.32, respectively. In nearly two-thirds of the families, the heaviest and the lightest triplet had a birth weight discordance over 15%. The NTR sample is representative for the Dutch triplet population that is still alive 28 days after birth.Conclusion: Birth weight is an important determinant of childhood development. Triplet status, gestational age, sex, zygosity and maternal smoking affect birth weight. The combined effects amount to a difference of 364 grams between monozygotic girl triplets of smoking mothers compared to dizygotic boy triplets of non-smoking mothers of the same gestational age. Birth weight in triplets is also influenced by genetic factors, as indicated by a larger correlation in monozygotic than in di- and trizygotic triplets

Herbal supplements in the print media: communicating benefits and risks

Background The rise in use of food supplements based on botanical ingredients (herbal supplements) is depicted as part of a trend empowering consumers to manage their day-to-day health needs, which presupposes access to clear and accurate information to make effective choices. Evidence regarding herbal supplement efficacy is extremely variable so recent regulations eliminating unsubstantiated claims about potential effects leave producers able to provide very little information about their products. Medical practitioners are rarely educated about herbal supplements and most users learn about them via word-of-mouth, allowing dangerous misconceptions to thrive, chief among them the assumption that natural products are inherently safe. Print media is prolific among the information channels still able to freely discuss herbal supplements. Method This study thematically analyses how 76 newspaper/magazine articles from the UK, Romania and Italy portray the potential risks and benefits of herbal supplements. Results Most articles referenced both risks and benefits and were factually accurate but often lacked context and impartiality. More telling was how the risks and benefits were framed in service of a chosen narrative, the paucity of authoritative information allowing journalists leeway to recontextualise herbal supplements in ways that serviced the goals and values of their specific publications and readerships. Conclusion Providing sufficient information to empower consumers should not be the responsibility of print media, instead an accessible source of objective information is required.</p

Les inventaires anciens de bibliothèques médiévales françaises

L’équipe de « Codicologie, histoire des bibliothèques et héraldique » de l’Institut de recherche et d’histoire des textes (IRHT) a lancé depuis 2006 le programme « BMF. Bibliothèques médiévales de France », dont l’ambition est de mettre à la disposition des chercheurs et du public l’ensemble des sources permettant de reconstituer les collections de manuscrits de la France médiévale et d’Ancien Régime. Ce n’est pas une idée nouvelle : cet objectif est à l’origine même de la section de Codicolo..

Les inventaires anciens de bibliothèques médiévales françaises

L’équipe de « Codicologie, histoire des bibliothèques et héraldique » de l’Institut de recherche et d’histoire des textes (IRHT) a lancé depuis 2006 le programme « BMF. Bibliothèques médiévales de France », dont l’ambition est de mettre à la disposition des chercheurs et du public l’ensemble des sources permettant de reconstituer les collections de manuscrits de la France médiévale et d’Ancien Régime. Ce n’est pas une idée nouvelle : cet objectif est à l’origine même de la section de Codicolo..

First evidence of Seoul hantavirus in the wild rat population in the Netherlands

We report the first detection of Seoul hantavirus (SEOV)-specific antibodies in the wild brown rat population in the Netherlands. SEOV-reactive antibodies were found in three rats out of 16 in a repeated series of tests including immunofluorescence assay, immunoblot, and enzyme-linked immunosorbent assay. Focus reduction neutralization test confirmed the presence of SEOV-specific antibodies, and reverse-transcription polymerase chain reaction (RT-PCR) confirmed the presence of hantaviral RNA. This discovery follows the recent findings of SEOV infections in wild and pet brown rats and humans in England, Wales, France, Belgium, and Sweden, indicating an even higher importance of this hantavirus for public health in large areas of Europe