Context: Acid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown. Objective: To investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers. Subjects: Three short Kurdish brothers and their relatives. Results: The index cases presented with short stature, microcephaly, and low circulating IGF-I and IGFbinding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives. Conclusions: The clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect.

BACKGROUND: Reference data for physical activity level (PAL) and activity-related energy expenditure (AEE) are needed for a better understanding of the effect of activity on childhood health, growth and development OBJECTIVE: Data from 17 studies measuring TDEE (TDEE) with doubly labelled water DLW were combined to construct a reference line for PAL and AEE as a function of age. DESIGN: A total of 17 studies from the literature were analyzed; 17 on girls and 16 on boys. Children were aged 3-16 y and of Caucasian origin. Weighted least-squares regression was used to obtain reference lines for PAL and AEE as a function of age and gender. The relative numbers of children per study were used as a weighting factor. Basal metabolic rate (BMR) or nonfasted (NF) resting metabolic rate and sex were included in the analysis. RESULTS: Although there was no difference in PAL between boys and girls, a significant difference in AEE was found between the two sexes. PAL: 0.025 Â age+1.40. AEE (MJ/day): boys 0.30 Â age+0.025; girls 0.21 Â age+0.33. If BMR is measured under NF conditions, the obtained value has to be reduced by 0.21 for PAL and 0.75 MJ/day for AEE. No relation was found between AEE/kg and age. CONCLUSIONS: PAL and AEE were found to increase with age, showing the importance of age-dependent recommendations. Recommendations for AEE need to be differentiated for sex. To compare PAL and AEE between studies, the measurement conditions of BMR have to be taken into account. The increase in PAL and AEE values can be attributed to an increase in weight, because there was no relation between AEE/kg and age.

Objectives: Accelerometry was used to assess the relationship between the physical activity level (PAL) and time spent on activities of various intensities in children. Design: A total of 20 children aged 8.673.3 y wore a triaxial accelerometer (Tracmor2) for 2 weeks. PAL was calculated with Tracmor2 output data. The fraction of time spent on activities with a given level of intensity (low, moderate, high) was calculated. The fractions of time spent on activities of different intensities were compared with previously obtained data for young adults and elderly persons. Results: PAL showed an inverse relation with the percentage of time spent on low-intensity activities (r ¼ À0.76; Po0.0001) and a positive relation with the percentage of time spent on high-intensity activities (r ¼ 0.93; Po 0.0001). The fraction of time spent on low-intensity activities was smaller in children than in young adults (Po0.05) and elderly persons (Po0.0001), while the fraction spent on high-intensity activities (Po0.0001) was larger. Conclusions: The present data are important for a better understanding of physical activity in children, which is necessary for education and prevention about physical (in)activity in childhood. Our observations suggest that to obtain a higher PAL in children, they should be given the opportunities to perform high-intensity activities.

Despite the shortcomings of an anthropometric approach in estimating the fraction of fat-free mass or protein content, its simplicity makes the method of calculating these fractions on skinfold thicknesses and mid-upperarm circumference valuable to apply in daily paediatric practice.

A widely used method of judging body proportions is to consider the ratio of sitting height to height (SH/H) related to age. A drawback of this method is that only one derived variable is used. A pairwise consideration of the original measurements provides more information. In this study data from the cross-sectional Oosterwolde I growth study are used to present normal values for the ratio SH/H for age, as well as values for sitting height related to height and subischial leg length. A comparison is made with other studies.