SOFT syndrome with kohlschutter-Tonz syndrome.

We report a 2.2 year-old-boy, born of consanguineous marriage, referred for short stature, with history of neonatal death and skeletal deformities in his older sibling. Rhizo-mesomelic dwarfism was detected antenatally. Within 24 hours of birth, he developed multiple seizures. Examination revealed severe short stature, dolichocephaly, broad forehead, deep set eyes, low set ears, bulbous nose, small, irregular teeth, pointed chin, and triangular facies. He had rhizomelic shortening, stubby fingers, pes planus, and scanty hair. Neurological evaluation revealed ataxia, hypotonia, and global developmental delay. Skeletal survey radiograph revealed shallow acetabuli, short femurs and humerus, short, broad metacarpals and short cone-shaped phalanges with cupping of phalangeal bases. Clinical exome analysis revealed homozygous mutations involving the POC1A gene and the SLC13A5 gene responsible for SOFT syndrome and Kohlschutter-Tonz syndrome respectively, which were inherited from the parents. Both these syndromes are extremely rare, and their co-occurrence is being reported for the first time.

Body fat indices for identifying risk of hypertension in Indian children.

BACKGROUND: High adiposity is major risk factor for hypertension. Various anthropometric indices are used to assess excess fatness. OBJECTIVES: (1) To examine relationship of body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), triceps skin fold thickness (TSFT) and wrist measurements with blood pressure in children and adolescents 2) to suggest age- and gender-specific cutoffs for these indices in Indian children. METHODS: Cross-sectional school-based study on a random sample of 6380 children (6-18 yr old, 3501 boys) from five major cities in India. Height, weight, waist and wrist circumference, TSFT, and blood pressure were recorded. Children with systolic blood pressure (BP) and/or Diastolic BP >95th percentile were classified as hypertensive. RESULTS: Prevalence of overweight and obesity was 23.5% and 9.7%, respectively. Hypertension was observed in 5.6%. Multiple logistic regression (adjustments: age, gender) indicated double risk of hypertension for overweight and 7 times higher odds for obese than normal-weight children. Children with TSFT >95th centile for US children showed three times risk and with TSFT from 85th to 95th double risk of hypertension. Higher WC and WHtR exhibited 1.5 times risk and larger Wrist 1.3 times higher risk of hypertension (P<0.001). Receiver operating curve (ROC) analysis provided age-gender specific cut offs for the five indices to detect the risk of high BP. Area under ROC curves (AUC) for five indices were similar and greater in older age groups indicating equal sensitivity and specificity. Conclusion: Using age- and gender-specific cutoffs for BMI, TSFT, WC or WHtR may offer putative markers for early detection of hypertension. CONCLUSION: Using age- and gender-specific cutoffs for BMI, TSFT, WC or WHtR may offer putative markers for early detection of hypertension.

Body fat reference percentiles on healthy affluent Indian children and adolescents to screen for adiposity.

BACKGROUND: Indian children and adolescents have higher body fat percentage at a given body mass index than their Western counterparts. OBJECTIVE: To create gender-specific percentile curves for total body fat percentage (TBFP), total body fat mass (TBFM), fat mass index (FMI) and android:gynoid (A:G) ratio for screening adiposity in healthy Indian children. METHODS: Data on body composition by dual-energy X-ray absorptiometry were obtained from a cross-sectional study conducted from May 2006-July 2010 on 888 (462 boys) apparently healthy children from affluent area schools and colleges in Pune city, India. Reference percentile curves were derived for boys and girls for TBFP, TBFM, FMI and A:G ratio. These percentile curves were validated using data on metabolic syndrome risk components in separate sample of 332 (148 boys) children. RESULTS: The median TBFP increased little (4%) from 5 to 18 years of age in boys compared with that in girls (19%). TBFP percentiles showed plateau after 13 years of age in boys, whereas a steady increase was seen till 18 years in girls. The median TBFM increased less (7 kg) from 5 to 18 years in boys compared with that in girls (13.4 kg). The curve for median FMI in boys was relatively flat with FMI remaining near 3 kg m(-2) after 13 years of age, whereas in girls median FMI increased with age till about 15 years of age. A:G ratio curves increased with age in both boys and girls up to 18 years of age. In a separate sample of 332 children, according to percentiles developed in the current study, children with TBFP/TBFM/FMI percentiles between 85th and 95th or >95th percentile had significantly higher metabolic risk parameters as compared with those with <85th percentile (P<0.05). CONCLUSIONS: Percentile curves developed in the current study would be useful in assessment of adiposity and thus cardiometabolic risk in Indian children.

Relationship between body mass index, fat distribution and cardiometabolic risk factors in Indian children and adolescents.

BACKGROUND: Studies assessing the relationship of BMI and BF with cardiometabolic (CM) risks in Indian children are scarce. OBJECTIVE: To assess the occurrence of cardiometabolic risk factors in Indian children and adolescents in relation to BMI and body fat and to study their association with body fat distribution. METHODS: 286 children and adolescents (mean age 11.2 ± 2.6 years, 139 boys) were recruited from routine health checks and schools. Anthropometry and blood pressure were recorded, total body fat (BF) and fat distribution (android and gynoid) were measured by Dual Energy X-ray Absorptiometry. Fasting plasma glucose, lipid profile and insulin were also measured. RESULTS: When the study cohort was divided as per their BMI and biochemical cardiometabolic risk factors, 8% children had normal BMI with abnormal biochemical parameters while 40% children had abnormal BMI but normal biochemical parameters. CONCLUSION: There are normal weight children with cardiometabolic risks. There was an increase in the occurrence of cardiometabolic risk factors with increased android distribution of fat (p-value < 0.05).

Body mass index cut-offs for screening for childhood overweight and obesity in Indian children.

OBJECTIVE: To develop age and sex specific cut offs for BMI to screen for overweight and obesity in Indian children linked to an adult BMI of 23 and 28 kg/m2 respectively, using contemporary Indian data. DESIGN: Cross-sectional. SETTING: Multicentric, School based. PARTICIPANTS: 19834 children were measured from 11 affluent schools from five major geographical regions of India. Data were analyzed using the LMS method, which constructs growth reference percentiles adjusted for skewness. RESULTS: Compared to the cut-offs suggested for European populations and those by the Indian Academy of Pediatrics 2007 Guidelines, the age and sex specific cut off points for body mass index for overweight and obesity for Indian children suggested by this study are lower. CONCLUSIONS: Contemporary cross-sectional age and sex specific BMI cut-offs for Indian children linked to Asian cut-offs of 23 and 28 kg/m2 for the assessment of risk of overweight and obesity, respectively are presented.

Efficacy of a continuous metabolic syndrome score in Indian children for detecting subclinical atherosclerotic risk.

OBJECTIVE: To evaluate the continuous metabolic syndrome score (cMetS) in Indian children and to investigate its relationship with the risk of carotid arterial stiffness. METHODS: Data on weight, height, mean arterial pressure, serum lipids, insulin, glucose, carotid intima-media thickness and stiffness parameters, that is, pulse wave velocity (PWV), elasticity modulus (Ep), stiffness index (ß) and arterial compliance (AC), were assessed in 236 children (6-17 years) from Pune city, India. cMetS was computed using standardized Z-scores for metabolic syndrome (MS) components. cMetS cutoff was obtained by receiver operating characteristic curve analysis across MS components. RESULTS: cMetS was lowest (-3.6±2.0) in normal children and highest (3.3±2.4) in MS children. cMetS increased progressively with number of risk components. The cutoff of cMetS yielding maximal sensitivity (80%) and specificity (94%) for predicting the presence of MS was -0.8 (area under the curve=0.921 (95% CI: 0.877-0.964)). In children with cMetS above -0.8, average PWV (4.3±0.6 m s(-1)), ß (3.8±1.2) and Ep (50.4±14.5 kPa) were significantly higher than the respective values (3.7±0.5 m s(-1); 3.4±0.8; 37.0±10.0 kPa) in children with cMetS below -0.8, whereas AC was lower (1.2±0.5 mm(2) kPa(-1)) in children with cMetS above -0.8 as against AC (1.4±0.3 mm(2) kPa(-1)) in children with cMetS below -0.8 (P<0.05), demonstrating the risk of stiffness with increasing score. Pearson's correlation coefficients of cMetS with PWV (r=0.575), ß (r=0.347), AC (r=-0.267) and Ep (r=0.530) were statistically significant (P<0.01). CONCLUSION: Results demonstrate the usefulness of cMetS over individual MS components as a better tool for assessment of atherosclerotic risk in children.

A pilot randomized controlled trial of oral calcium and vitamin D supplementation using fortified laddoos in underprivileged Indian toddlers.

BACKGROUND/OBJECTIVES: Low habitual dietary calcium intake and vitamin D deficiency are common among Indian children. Using 'laddoo', an Indian snack, as a vehicle for administering calcium and vitamin D supplements, a randomized double-blind controlled trial was conducted for 12 months to assess its efficacy on total body less head (TBLH) bone mineral content (BMC) in underprivileged toddlers. SUBJECTS/METHODS: A total of 60 toddlers (mean age 2.7±0.52 years, boys=31) were randomized to two groups, (i) study group receiving one calcium fortified laddoo (cereal-legume snack) containing 405 mg calcium per day and (ii) control receiving a non-fortified laddoo, containing 156 mg of indigenous calcium. Both groups also received a laddoo fortified with 30,000 IU of vitamin D(3) per month. Outcome measures included TBLH bone area (BA) and TBLH BMC by GE-Lunar DPX Pro Pencil Beam Dual-Energy X-ray absorptiometry. RESULTS: At baseline, mean energy, protein and calcium intakes were 71, 72 and 47% of Indian Recommended Dietary allowances. In all, 87 and 83% toddlers were hypocalcaemia and vitamin D deficient, respectively. Mean TBLH BMC was 289.5±45.8 g. Post supplementation, mean TBLH BMC of study group showed a significantly greater (P<0.01) increase of 35% as against 28% in controls and the difference remained significant after adjusting for vitamin D status, calcium intake, height and TBLH BA. CONCLUSIONS: Daily supplementation with calcium fortified laddoo, and monthly vitamin D supplement resulted in a significant increase in TBLH BMC of underprivileged toddlers. We believe that such strategies have the potential of addressing nutritional problems in developing countries.

Overweight and obesity prevalence and body mass index trends in Indian children.

OBJECTIVES: To estimate prevalence of overweight and obesity in apparently healthy children from five zones of India in the age group of 2 to 17 years and to examine trends in body mass index (BMI) during the last two decades with respect to published growth data. METHODS: A multicentric study was conducted in eleven affluent urban schools from five geographical zones of India. A total of 20 243 children (1 823 - central zone, 2 092 - east zone, 5 526 - north zone, 3 357 - south zone, and 7 445 - west zone) in the age group of 2-17 years were studied. Height and weight were measured and BMI was calculated (kg/m(2)). WHO Anthro plus was used to calculate Z-scores for height, weight and BMI. A comparison between study population and previously available nationally representative (1989) data was performed for each age-sex group. International Obesity Task Force (IOTF) and WHO cut-offs were used to calculate the percentage prevalence of overweight and obesity. RESULTS: The overall prevalence of overweight and obesity was 18.2% by the IOTF classification and 23.9% by the WHO standards. The prevalence of overweight and obesity was higher in boys than girls. Mean BMI values were significantly higher than those reported in the 1989 data from 5-17 years at all ages and for both sexes. CONCLUSION: The rising trend of BMI in Indian children and adolescents observed in this multicentric study rings alarm bells in terms of associated adverse health consequences in adulthood.

KCNJ11 activating mutation in an Indian family with remitting and relapsing diabetes.

OBJECTIVE: To identify the genetic cause of transient neonatal diabetes mellitus in three siblings from an Indian family. METHODS: Case reports with clinical and molecular evaluation of an activating mutation in the KCNJ11 gene are presented. We describe an Indian family with two asymptomatic parents with 3 children presenting with hyperglycemia at 6, 1.5 and 1 month of age respectively. Blood glucose levels at presentation were 22.2, 18.3 and 20 mmol/L and the diabetes remitted in all three children by 5 years of age. None of the affected siblings had dysmorphism or neurological abnormalities. Diabetes relapsed in the oldest sibling at 9.4 years of age and she is now euglycemic on 1mg/Kg of Glibenclamide twice a day. RESULTS: A novel heterozygous missense mutation (G53V) in the KCNJ11 gene was identified in all 3 affected children and the father. CONCLUSIONS: Our report suggests that screening for KCNJ11 mutations is appropriate in patients diagnosed with neonatal diabetes as it provides valuable information concerning possible course of the disease and choice of treatment.

Growth performance of affluent Indian preschool children: a comparison with the new WHO growth standard.

This study was conducted to evaluate the nutritional status of 2-5 year old affluent, urban children using the new WHO 2006 standards. A cross-sectional, multicentric preschool-based study was conducted on 1493 children (727 boys). Mean Z scores for height, weight, body mass index and weight for height(-0.75(1.1), -0.59(1.1), -0.19(1.22) and -0.26(1.18), respectively) were below the WHO standard median.

Sunlight exposure and development of rickets in Indian toddlers.

OBJECTIVE: To study the role of sunlight exposure in determining the vitamin D status of underprivileged toddlers. METHODS: Height and weight were measured, clinical examination was performed, Food Frequency Questionnaire was administered and history of sunlight exposure was obtained in all (61) toddlers attending daytime crèche (Group B). Ionised calcium (iCa), inorganic Phosphorous (iP), alkaline phosphatase activity (ALP), serum parathyroid hormone (PTH) and 25 Hydroxy vitamin D (25OHD) were measured. Data were compared with results of a survey measuring similar parameters in 51 (of 251 eligible) toddlers from the same slum (Group A). RESULTS: 111 children (mean age 2.6 yr (0.7), boys 56) were studied. Prevalence of hypovitaminosis D was 77% in group B toddlers (46 of 60) and 16.4% (10 of 61) had rickets, while none of the group A toddlers had 25OHD levels below 30 nmol/L. Four children (7.8%) from Group A as against 24 (42.9%) from Group B, had sunshine exposure of < 30 minutes per day. CONCLUSION: Underprivileged toddlers who were deprived of sunlight had a much greater incidence of hypovitaminosis D and frank rickets. The study has important public health implications and underscores the necessity for sunlight exposure in young children.

Bone status of adolescent girls in Pune (India) compared to age-matched South Asian and white Caucasian girls in the UK.

UNLABELLED: Underprivileged adolescent girls in Pune, India, were shorter and lighter, and had reduced lean body mass (LBM) compared with relatively 'well off' age-matched South Asian and white Caucasian girls in the UK. Pune girls had low bone mass for projected bone area (BA) in comparison to their UK counterparts, but they had the appropriate amount of bone mineral content (BMC) for their LBM. PURPOSE: To determine whether adolescent girls from a low socioeconomic group in Pune, India, who had low dietary calcium intake (449 mg/day; range 356-538 mg/day) and hypovitaminosis D (median serum 25-hydroxyvitamin D 23.4 nmol/l; range 13.5-31.9 nmol/l), would have lower lumbar spine (LS) bone mineral apparent density (BMAD), and total body (TB) BMC adjusted for LBM. METHODS: Dual energy X-ray absorptiometry was used to measure TB and LS BMC, BA and TB LBM in 50 postmenarcheal girls in Pune. These variables were compared with data from 34 South Asian and 82 white Caucasian age-matched girls in the UK. RESULTS: Pune girls were shorter and lighter, and had less LBM for height, compared to both UK groups, and they had later age of menarche than UK Asians. BA-adjusted TB BMC and LS BMAD were lower in Pune girls (mean+/-SE 1,778+/-17 g; 0.332+/-0.005 g/cm(3)), compared to the UK South Asians (mean+/-SE 1,864+/-18 g; 0.355+/-0.006 g/cm(3)) and UK white Caucasians (mean+/-SE 1,864+/-13 g; 0.345+/-0.004 g/cm(3)). In contrast both LS and TB BMC adjusted for TB LBM were not significantly different between the groups. CONCLUSION: Pune girls had low bone mass for projected BA relative to UK South Asian and white Caucasian girls, but had the appropriate amount of BMC for their LBM.

Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers.

BACKGROUND: Toddlers in Pune, India, accustomed to low dietary calcium intake but vitamin D replete have low serum ionised calcium and inappropriately raised serum inorganic phosphorus concentrations together with elevated serum parathyroid hormone (PTH) concentrations. We hypothesised that dietary calcium deficiency leads to end organ resistance to PTH, thus resulting in mild hypocalcaemia and hyperphosphataemia, and that this would be reversed by oral calcium supplementation. METHODS: 51 subjects (25 male; mean (SD) age 2.4 (0.8) years) from an urban slum in Pune were randomised to 500 mg of oral calcium supplement or placebo, daily, for 8 weeks. All subjects received 20 mg of oral elemental iron, daily, as 90% had a serum ferritin concentration <12 microg/l. All subjects were examined for clinical stigmata of rickets and had a wrist radiograph performed. Serum concentrations of ionised calcium, phosphorus, PTH and fibroblast growth factor-23 (FGF-23) were measured at the start and end of the trial. RESULTS: No subject had clinical or radiological evidence of rickets. There was a significant increase in mean serum ionised calcium concentration (p<0.001) in the supplemented but not the placebo group (p = 0.32). The decrease in mean serum phosphorus concentration in the supplemented group was greater (p<0.001) than in the placebo group (p = 0.003). Mean serum PTH fell in the calcium supplemented (p = 0.001) but not in the placebo (p = 0.303) group. The mean serum FGF-23 concentration did not change in response to calcium supplementation. CONCLUSIONS: From these data the authors conclude that low dietary calcium intake is associated with resistance to PTH.

Crosssectional growth curves for height, weight and body mass index for affluent Indian children, 2007.

BACKGROUND: The assessment of growth is crucial in child care and reference data are central to growth monitoring. As the pattern of growth of a population changes with time it is recommended that references be updated regularly. OBJECTIVE: To produce contemporary growth curves for Indian children from 5-18 years for height, weight and BMI. DESIGN: Cross-sectional. SETTING: Multicentric, School based. PARTICIPANTS: 19834 children were measured from 10 affluent schools from five major geographical regions of India. Data were analyzed on 18666 children (10496 boys and 8170 girls) using the LMS method and smoothed percentiles 2007 were produced. RESULTS: Compared to the 1989 data, median height at 18 years was 0.6 cm greater for boys but unchanged for girls, while the 97th height percentile had increased by 1.7 cm for boys and 2 cm for girls. Boys and girls were heavier and taller at almost all ages. The study also showed that boys and girls were taller at a younger age. CONCLUSIONS: Contemporary cross sectional reference percentile curves for height, weight and body mass index for the assessment of physical growth of present day Indian children are presented.

Bone disease in preterm.

The survival rate of premature infants has significantly increased during the last few decades. As a consequence, new disorders such as osteopenia of prematurity have been emerging. We report 6 month evolution from diagnosis to recovery of a patient with metabolic bone disease of prematurity who showed a remarkable improvement on therapy with phosphate, calcium and vitamin D.

Allgrove syndrome.

Allgrove syndrome consists of triad of Adrenal hypoplasia, Achalasia cardia and Alacrimia. Often the first manifestation of adrenal hypoplasia is Addisonian crisis precipitated by infection or trauma. We present case of a 9-year-old boy who presented in shock due to adrenal failure later confirmed to have Allgove syndrome.