The most common form of familial hyposphatemic rickets (FHR), a group of disorders with similar clinical and biochemical features [hypophosphatemia, hyperphosphaturia, normal levels of 1,25(OH)2D3 and PTH, skeletal deformities, short stature, osteomalacia, dental abscesses bone pain], is represented by the dominant X-linked hyposphatemic rickets (XLH). Individuals with FHR phenotype and a negative familial history in 60-80% of cases are carriers of mutations in PHEX gene, on chromosome Xp22.2-p22.1. The mice phenotypical analogue of the human XLH is represented by Hyp strand, in which a 3’ deletion of Phex removes its COOH-terminal domain. The clinical consequences of PHEX inactivating mutations indicate that its encoded product, an endopeptidase member M13Zn-metallopeptidases family, expressed at the skeletal level by osteoblasts, osteocytes, and odontoblasts, is involved in phosphate regulation and mineral homeostasis. PHEX inactivating mutations widespread along the gene, cause XLH: exons 3-411-12-14-15-17-20-22 represent the regions with the higher rate of mutation; such mutations could enable the accumulation of phosphaturic factors and/or mineralization inhibitors. A 26 years old male patient (height 176cm, weight 65 kg) referred to our Centre exhibiting a clear hyperphosphaturia (>2000 mg/24h), hypophosphatemia, hypercalciuria (>600 mg/24h), hypocalcemia (• 8,1 mg/die), PTH circulating levels at the upper values of the normal range and normal values of 25(OH)D; other symptoms were: deep asthenia, muscle pain and spasms, abundant diuresis (• 2,5 lt/die). After obtaining the signed informed consent we performed a blood sampling from which genomic DNA has been prepared to analysed PHEX gene. The 22 exons and the intron-exon boundaries of PHEX gene have been investigated by a PCR/Sequencing protocol (ABI-Prism 3100). It has been determined the presence of a hemizygous missense mutation of PHEX gene in codon 401 (CCT/CTT) causing a Pro/Leu substitution in the extracellular domain closely a cysteine residue highly conserved in exon 11. Nearly future functional studies will be helpful to characterize the molecular mechanisms underlying this mutation.

Tumoral calcinosis (TC) is a rare genetic disorder characterized by periarticular cystic and solid tumorals calcifications. Biochemical markers of disorder include hyperphosphatemia and an elevated serum of calcitriol concentration in every patients. The hyperphosphatemia results form an increase in capacity of renal tubular phosphate reabsorption. The identification of phosphotonin family hormones suggest that mutations of these molecules could be involved in the pathogenesis of TC. One of these molecules is represented by FGF-23. Recently, biallelic mutation on the GalNAc transferase 3 or GALNT3 gene has been established as the molecular cause of recessive forms of TC. In the present study we described a new FGF-23 mutation in a subject affected by TC without mutations of GALNT3 gene. A Caucasian women (years 67) was examined for a history of ectopic calcification. Biochemical exams showed and hyperphosphathemia and hyperphosphaturia with normal value of PTH and 1-25(OH)2 D3. The patient presented a shoulder calcification and also a calcification of femoral artery. The family tree history revealed that parents were consanguineous. Hystologically the mass was characterized by calcium deposition and granulomatous reaction around the mass. Genomic DNA was extracted from blood collected from the patient, her daughter and her grandchild by standard procedure. DNA was not available from her parents. All three FGF-23 coding exons, as well as conserved splice sites, were amplified by standard PCR procedure. Nucleotide sequences were determined by direct sequencing with a DNA kit and an automated DNA sequencer (ABI PRISM 3100 Perkiln-Elmer Corp). We discovered a new homozygous codon 41, His/Gln (CAC-CAA) substitution in exon 1 of FGF-23 gene in the affected patient. A heterozygous substitution was present in the daughter. No mutation were found in the two children. FGF-23 gene mutation was not found in the SNP database (www.ncbi.nih.gov/snp). In summary, a recessive mutation in FGF-23 causes TC. Understanding the functional significance and molecular physiology of this novel mutation will reveal critical information regarding the role of FGF-23 in states of normal and of disorder of phosphate homeostasis.

Osteporosis is a condition of skeletal fragility characterized by reduced bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fractures. Several factors, endogenous and exogenous, are involved in the achievement of bone during growth and in the pathogenesis of bone loss. Calcium and vitamin D are commonly considered very important for bone health and a low calcium intake is a risk factor for osteoporosis. The aim of the present study was to evaluate the amount of calcium, vitamin D, antinutrients (fibers and proteins) in a population of osteoporotic women. The cohort comprised 110 postmenopausal Italian women aged 62±8.4 years affected by osteoporosis and recruited among women attending the outpatient of the Metabolic Bone Disease Unit of Florence. Dietary pattern was assessed by trained dietitians through a semiquantitative food questionnaire. In order to evaluated the dietary intake of micro and macronutrients derived by the questionnaire we used the Winfood software (Winfood 2). The results showed that the mean daily amount of Kcal was 1910±223. The Kcal were represented by proteins 16.2% (77.3±12.8 g/day), fats 31% (65.7±14 g/day) and sugars 53% (257±42 g/day). The amount of fibers was 21.3±5 g/day, under the recommended levels. The daily amount of calcium intake was 800±296 mg/day, which was lower than the recommended levels for postmenopausal women. A very low amount of vitamin D intake was found in this population (1.55±0.88 µg/day; recommended value: 10 µg/day). In conclusion, this nutritional data indicate an insufficient amount of calcium and vitamin D intake in the postmenopausal osteoporotic women.

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder.