Glucokinase mutations in pediatric patients with impaired fasting glucose.

AIMS: Our aim was to detect the frequency of glucokinase (GCK) gene mutations in a cohort of patients with impaired fasting glucose and to describe the clinical manifestations of identified variants. We also aimed at predicting the effect of the novel missense mutations by computational approach. METHODS: Overall 100 unrelated Italian families with impaired fasting glucose were enrolled and subdivided into two cohorts according to strict and to mild criteria for diagnosis of maturity-onset diabetes of the young (MODY). GCK gene sequencing was performed in all participants. RESULTS: Fifty-three Italian families with 44 different mutations affecting the GCK and co-segregating with the clinical phenotype of GCK/MODY were identified. All mutations were in heterozygous state. In Sample 1, GCK defects were found in 32/36 (88.9%) subjects selected with strict MODY diagnostic criteria, while in Sample 2 GCK defects were found in 21/64 (32.8%) subjects selected with mild MODY diagnostic criteria. CONCLUSIONS: Our study enlarged the wide spectrum of GCK defects by adding 9 novel variants. The application of strict recruitment criteria resulted in 88.9% incidence of GCK/MODY, which confirmed it as the commonest form of MODY in the Italian population. In order to avoid misdiagnosis of GCK/MODY, it could be useful to perform molecular screening even if one or more clinical parameters for the diagnosis of MODY are missing. Computational analysis is useful to understand the effect of GCK defect on protein functionality, especially when the novel identified variant is a missense mutation and/or parents' DNA is not available.

Longitudinal assessment of bone quality by quantitative ultrasonography in children and adolescents.

Among the techniques available to assess bone quality, quantitative ultrasonography of the proximal phalanges of the hand (QUS) has emerged as particularly attractive. In this study, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were obtained by the sonographic device DBM Sonic BP IGEA in two sessions at two years' interval, in a school-age population (589 subjects, 290 mol/L and 299F, aged 3 to 16 y) with the aim to determine accuracy of QUS measurements, evaluate QUS variable changes during growth, relate these values with age and growth variables. Mean AD-SoS and BTT at age classes from 5 to 12 y as determined at the first and second measurement sessions were not significantly different. A significant increment (p < 0.0001) between the first and the second measurement was observed for both QUS variables. AD-SoS and BTT showed significantly different variations in the various age groups (ANOVA). Correlations were found of AD-SoS and BTT increments with age, height, weight, pubertal stage and with height growth velocity (p < 0.05). AD-SoS and BTT increment curves presented a very similar trend decreasing from 4 to 7 y of age. Thereafter a plateau was reached up to the age of 10 to 11 y in girls and 11 to 12 y in boys, when an increase was observed corresponding to pubertal growth rate acceleration. In conclusion, the present study would confirm that QUS measurements are accurate. Ad-SoS and BTT increment models are similar to most growth velocity curves and follow a strongly age- and growth-dependent pattern.

Influence of age, sex, and growth variables on phalangeal quantitative ultrasound measures: a study in healthy children and adolescents.

Skeletal status by phalangeal quantitative osteosonography (DBM Sonic BP-IGEA) was examined in 1227 healthy children (641 boys and 586 girls) aged 3-16 years. Aims of the study were to evaluate some physical parameters pertaining to the ultrasound transmission crossing the phalanx in a school-age population and to relate these values to age, sex, and growth variables. A correlation was found between AD-SoS (amplitude-dependent speed of sound) and BTT (bone transmission time) and, age, height, weight, and pubertal stage, respectively. No correlation existed between FWA (fast wave amplitude) and SDy (dynamics of the ultrasound signal) and age, height, weight, pubertal stage, and BMI, respectively. AD-SoS increased in boys until 7-8 years of age. Thereafter a plateau was reached up to age 12-13 years, when a rapid increase was observed corresponding to pubertal growth rate acceleration. In girls, AD-SoS increased with age up to 10-11 years with a steeper increase at the time of puberty starting about 2 years earlier than in boys. BTT presented a similar trend. Mean AD-SoS values increased from Tanner pubertal stages 1 to 2 and from stage 3 to 4 in both sexes. Significantly higher mean AD-SoS values in stages 2, 3, and 4 were observed in girls as compared to boys. Mean BTT values increased significantly from stage 1 to 5 in girls and from 1 to 4 in boys. QUS technology showed the ability to assess bone changes in the growing bone.