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.

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.

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.