Intranasal treatment of vitamin B12 deficiency in children.

Vitamin B12 deficiency is traditionally treated with intramuscular injections of cobalamin, which are stressful events for children. In adults, studies have shown adequate absorption of intranasally administered vitamin B12. To date, data concerning efficacy of intranasal administration of vitamin B12 in children are lacking. We report on ten cases of children with vitamin B12 deficiency who were successfully treated with intranasal administration of a spray containing hydroxocobalamin. The mean baseline vitamin B12 concentration increased from 126.3 pmol/l (SD 55.4) to 1914.7 pmol/l (SD 1509.7). No side effects were reported.Conclusion: In children, intranasal application of vitamin B12 seems a safe and effective alternative to intramuscular injections, leading to higher compliance and less burden to patients.What is Known:• Children with vitamin B12deficiency are traditionally treated with intramuscular cobalamin injections, which are costly and painful.• Studies in adults showed that intranasal application of hydroxocobalamin leads to normalisation of vitamin B12levels.What is New:• The intranasal application of vitamin B12resulted in a substantial increase of the mean baseline vitamin B12levels without any side effect.• These data encourage a systematic evaluation of intranasal treatment of vitamin B12deficiency in order to define safety, optimal dosage and administration frequency.

A twin-sibling study on early growth and hormone levels in adolescents.

This study addresses how growth during sensitive developmental periods and genes may affect hormone levels in late adolescence. We analyzed hormone levels of dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor-I (IGF-I), which are hypothesized to be two pathways linking early growth with adult diseases (such as type 2 diabetes and cardiovascular disease) via their effects on enhanced insulin resistance. In a twin-sibling study, we tested whether there is an association between reduced intra-uterine growth and higher DHEAS or IGF-I levels in serum during adolescence, and we examined the contribution of insulin to the link between early growth and higher DHEAS and/or IGF-I levels. Anthropometric and hormone data were collected in 18-year-old twins (184 pairs) and their non-twin siblings (n = 98). Neither birth weight nor current body size predicted serum DHEAS and IGF-I levels. In the subsample of children who showed catch-up growth in weight during infancy, the children of lower birth weight had significantly higher serum DHEAS and IGF-I levels, but these were not related to insulin levels. Variation in serum DHEAS, IGF-I and fasting insulin levels was largely explained by genetic factors (73, 78 and 61 % respectively). Thus, early growth affects hormone levels in adolescence, but only in children with catch-up growth after birth. No evidence was found that early growth enhances insulin resistance via the hormones DHEAS or IGF-I.

Body size of twins compared with siblings and the general population: from birth to late adolescence.

OBJECTIVES: We examined whether and when differences in body size disappear over time and whether twins attain normal final height and body mass index (BMI). STUDY DESIGN: Height, weight, and BMI data of twins at ages 1, 4, and 18 years were compared with data from their nontwin siblings. Second, twin and sibling data were compared with population standards. In addition to height, weight, and BMI, data on body proportions at age 18 years were analyzed. RESULTS: At the age of 18 years, twins were as tall as their siblings but were significantly leaner. Compared with children from the general population, adolescent twins attained the same height and BMI. Birth weight was shown to have a considerable effect on height in adolescent twins. CONCLUSIONS: Twins attained normal final height compared with siblings and children from the general population. No differences in BMI were shown between 18-year-old twins and children from the general population, whereas the siblings of twins had increased BMI values compared with the general population.

Heritability of head size in Dutch and Australian twin families at ages 0-50 years.

We assessed the heritability of head circumference, an approximation of brain size, in twin-sib families of different ages. Data from the youngest participants were collected a few weeks after birth and from the oldest participants around age 50 years. In nearly all age groups the largest part of the variation in head circumference was explained by genetic differences. Heritability estimates were 90% in young infants (4 to 5 months), 85-88% in early childhood, 83-87% in adolescence, 75% in young and mid adulthood. In infants younger than 3 months, heritability was very low or absent. Quantitative sex differences in heritability were observed in 15- and 18-year-olds, but there was no evidence for qualitative sex differences, that is, the same genes were expressed in both males and females. Longitudinal analysis of the data between 5, 7, and 18 years of age showed high genetic stability (.78 > R(G) > .98). These results indicate that head circumference is a highly heritable biometric trait and a valid target for future GWA studies.

A twin study of cognitive costs of low birth weight and catch-up growth.

OBJECTIVE: To investigate whether there is an association between catch-up growth and cognitive performance in humans. STUDY DESIGN: Catch-up growth was defined as the change in weight standard deviation scores during the first 2 years of life. Cognitive performance was assessed with psychometric IQ tests, administered at ages 12 and 18 years. Data were collected in twin pairs, and analyses were carried out within pairs. RESULTS: There was a significant negative association between catch-up growth and IQ at both ages 12 and 18 years. CONCLUSIONS: A larger gain in weight during the first 2 years of life is associated with a lower IQ. However, catch-up growth is correlated with birth weight and this correlation may explain part of the association.

Heritability of testis size.

Testis size is an important feature of male pubertal development. The genetic and environmental contributions to variation in human testis size have hardly been studied. We estimated the heritability of human testicular size in a group of mono- and dizygotic twins and their non-twin brothers (145 twins and 20 brothers from 95 families). Participants were 18 years old on average and all had reached Tanner development stage 4 or higher. Dizygotic twins and their siblings had a larger mean testis volume than monozygotic twins and their siblings. There was significant familial resemblance, with higher correlations in monozygotic twin pairs (0.59) than in dizygotic twin and sibling pairs (0.34). Heritability was estimated at 59% (95% CI = 37-75%), but a model that excluded genetic influences and attributed all familial resemblance to shared environment, fitted the data only marginally worse. The finding of larger mean testis volume in dizygotic twins may be of interest for future research into the mechanisms underlying dizygotic twinning.

Similarities and differences in lipidomics profiles among healthy monozygotic twin pairs.

Differences in genetic background and/or environmental exposure among individuals are expected to give rise to differences in measurable characteristics, or phenotypes. Consequently, genetic resemblance and similarities in environment should manifest as similarities in phenotypes. The metabolome reflects many of the system properties, and is therefore an important part of the phenotype. Nevertheless, it has not yet been examined to what extent individuals sharing part of their genome and/or environment indeed have similar metabolomes. Here we present the results of hierarchical clustering of blood plasma lipid profile data obtained by liquid chromatography-mass spectrometry from 23 healthy, 18-year-old twin pairs, of which 21 pairs were monozygotic, and 8 of their siblings. For 13 monozygotic twin pairs, within-pair similarities in relative concentrations of the detected lipids were indeed larger than the similarities with any other study participant. We demonstrate such high coclustering to be unexpected on basis of chance. The similarities between dizygotic twins and between nontwin siblings, as well as between nonfamilial participants, were less pronounced. In a number of twin pairs, within-pair dissimilarity of lipid profiles positively correlated with increased blood plasma concentrations of C-reactive protein in one twin. In conclusion, this study demonstrates that in healthy individuals, the individual genetic background contributes to the blood plasma lipid profile. Furthermore, lipid profiling may prove useful in monitoring health status, for example, in the context of personalized medicine.

Genetic regulation of growth in height and weight from 3 to 12 years of age: a longitudinal study of Dutch twin children.

Human growth is a complex and poorly understood process. We studied the effect of genetic and environmental factors on height and body mass index (BMI, kg/m(2)) based on maternal reports at 3, 4, 5, 7, 10 and 12 years of age in a large longitudinal cohort of Dutch twins (7755 complete twin pairs at age 3). Several multivariate variance component models for twins were fitted to the data using the Mx statistical package. The first-born twin was taller until age 10 and heavier until age 12 than the second-born co-twin. Heritability estimates were high for height (a(2) = .58-.91) and BMI (a(2) = .31-.82), but common and unshared environmental factors were also important. The phenotypic correlations across the ages for height and BMI were mainly explained by correlated additive genetic factors (r(a) = .77-.96 for height and .43-.92 for BMI), but common (r(c) = .40-.84 and .09-.78, respectively) and specific environmental correlations (r(e) = .50-.81 and .42-.80, respectively) were also significant. Additive genetic factors decreased with increasing age difference for both height and BMI. However, the full Cholesky model, which does not make any assumptions regarding the underlying genetic structure, had the best fit. High genetic correlations across the ages, especially for height, may help further molecular genetic studies of human growth. Environmental factors affecting height and BMI during growth period are also important, and further studies are needed to identify these factors and test whether they interact with genetic factors.

Body size in five-year-old twins: heritability and comparison to singleton standards.

The aim of this study is to examine causes of individual differences in height, weight and body mass index (BMI) in 5-year-old children registered with the Netherlands Twin Register. In addition, we examine whether the results of twin studies can be expanded to the singleton population by comparing the data from twins to Dutch reference growth data and by looking at the twins' target height, which was derived from parental height. For 2996 5-year-old twin pairs, information on height and weight and on parental height was available. Univariate and bivariate genetic analyses of height and weight and univariate analyses of BMI were conducted. In order to compare the twins to the singleton population, standard deviation scores (SDS) for height, BMI and target height were calculated based on Dutch reference growth charts for the general population from 1997. Genetic influences were an important source of variation in height, weight and BMI and the main source of covariation between height and weight. Additive genetic factors accounted for 69% and 66% of the individual differences in height in boys and girls, respectively. For weight, heritability estimates were 59% in boys and 78% in girls and for BMI 34% and 74%. The influence of common environment on height was 25% and 27%, on weight 24% and 10% and on BMI 44% and 12% in boys and girls. The bivariate model showed a large overlap between the genes influencing height and weight. Genes explain 78% (in boys) and 76% (in girls) of the covariance between weight and height. At the age of 5 years, female twins were as tall as singleton children, while male twins were shorter than singletons. For both boys and girls, however, mean height SDS was 0.6 standard deviation scores below the mean target height. All twins had lower BMI than singletons. Twins grow fairly well compared to singletons, but they grow below their target height. This may be due to the above average height of twin parents.