Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serum concentration of 1,25-dihydroxylvitamin D (1,25-[OH]2D) in normal children and in children with inherited diseases of bone was compared by use of a competitive binding assay. Observed values were: in 12 normal children and adolescents, 37.1 +/- 1.9 pg per milliliter (mean +/- S.D.); in 14 patients with X-linked hypophosphatemic rickets treated with vitamin D2 and phosphate supplements, 15.6 +/- 7.8 (P less than 0.01 versus control); in six patients with autosomal recessive vitamin D dependency treated with vitamin D2, 9.5 +/- 2.9 (P less than 0.01 versus control); and in four untreated patients with autosomal dominant hypophosphatemic (non-rachitic) bone disease, 30.2 +/- 6.3 (not significantly different from the controls). The difference in bone disease between X-linked hypophosphatemia (severe) and hypophosphatemic bone disease (mild) at comparable low serum levels of phosphate implies that 1,25-(OH)2D and phosphate may have independent roles in the pathogenesis of defective bone mineralization.
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PMID:Serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with hereditary rickets or bone disease. 30 18

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient's condition.
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PMID:A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment. 143 10

Familial hypophosphatemia are either primitive disorders of renal phosphate handling, isolated as in X linked hypophosphatemic rickets (XLHR) or associated with alterations of renal handling of other solutes. They can also occur in the course of a number of other inherited diseases such as vitamin D dependent rickets type I or II and distal tubular acidosis. The molecular basis of most of these diseases are unknown. Chronic hypophosphatemia induces an alteration of bone mineralisation with rickets in children and osteomalacia in children and adults. Hypophosphatemia and the bone disease are most important in XLHR or VDDR. Treatment with oral phosphate and 1 alpha hydroxylated vitamin D metabolites, and in some cases calcium, tends to correct the hypophosphatemia and the bone disease. Treatment of the associated metabolic disorder in certain Fanconi syndromes can correct hypophosphatemia. In the forms associated with hypocalcemia, phosphate therapy is not indicated, but rather calcium therapy.
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PMID:[Hypophosphatemia of a genetic origin]. 164 Oct 53

Familial hypophosphatemic rickets is characterized by defective skeletal mineralization resulting in abnormal growth and development. The pathologic and radiologic correlates of this syndrome have been given some investigation, but the effect of this mineralization defect on bone mineral density has not been adequately assessed. We measured axial and appendicular bone mineral in 17 children (mean age 5.59 +/- 4.87) with familial hypophosphatemia at baseline and at 6-month intervals after initiation of therapy with vitamin D3 (calcitriol) and phosphate supplementation. Noninvasive quantitative techniques included single photon absorptiometry (SPA) of the radius, combined cortical thickness (CCT) of the second metacarpal, and quantitative computed tomography (QCT) of vertebral trabecular bone. Thoraco-lumbar and hand/wrist radiographs were qualitatively assessed for the prevalence and severity of osteosclerosis, rickets, and other parameters indicative of metabolic bone disease as well as skeletal age. Quantitative determinations of bone mineral by each technique were compared with normal values for age and sex, and individual standardized scores (z-scores) were calculated at each measurement interval. Standard scores were also calculated for bone age-adjusted mineral values. At baseline, spinal trabecular bone by QCT was not significantly different from normal values; however, measurements of peripheral cortical bone by either SPA or CCT were significantly lower than values for normal children of the same age and sex (P = 0.05 and P = 0.01, respectively). Following therapy with calcitriol and phosphate, peripheral bone mass was not shown to improve significantly when contiguous standard scores were compared even when values were adjusted for bone age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Familial hypophosphatemic rickets: bone mass measurements in children following therapy with calcitriol and supplemental phosphate. 249 95

Fifty-one patients aged 1 year to 56 years with metabolic bone disease underwent renal ultrasound. Medullary nephrocalcinosis was found in nine of 24 patients with X-linked hypophosphatemic rickets and is considered to be iatrogenic, related to vitamin D therapy. Another three in this group of 24 with both medullary and cortical increased renal echogenicity had suffered from repeated episodes of vitamin D intoxication and had secondary hyperparathyroidism. Nephrocalcinosis was less frequent in patients with treated vitamin D-dependent rickets or hypophosphatemic bone disease where generally smaller doses of vitamin D are given. Patients with pseudohypoparathyroidism, on small doses of vitamin D, had a normal renal ultrasound. In cystinosis and Fanconi's syndrome, the kidneys are small, echodense (both the cortex and medulla) with a tendency to cyst formation.
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PMID:Renal ultrasound in metabolic bone disease. 351 10

Vitamin D-resistant rickets (VDRR) in adults is characterized by low serum phosphorus and osteomalacia. Despite the disappearance of rickets after the closure of epiphyses, some adults with VDRR present with symptomatic bone disease while other are asymptomatic. In order to test the presumption that asymptomatic adults no longer have active bone disease, we have compared bone histology in 10 symptom-free adults to 6 age-comparable symptomatic adults presenting with bone pain and persistent deformities. Both groups had similar low serum phosphorus and increased serum alkaline phosphatase values. Serum calcium, parathyroid hormone, and vitamin D metabolite concentrations were not different in the two groups. Histomorphometric study of bone formation and resorption was made on undecalcified sections of iliac crest bone biopsies obtained after in vivo single or dual tetracycline labeling. Bone histology revealed that both groups of patients had comparable osteomalacia, as evidenced by increased amount of osteoid tissue, prolonged mineralization lag time, and reduced bone formation rate. Despite the presence of osteomalacia, the trabecular calcified bone volume was within or above normal values in the two groups, implying a remodeling imbalance between the rates of bone resorption and formation. The data show that despite the absence of symptoms and the disappearance of rickets, adults with VDRR still have active bone disease characterized by moderate to severe osteomalacia. The normal to increased trabecular bone mass implies that the occurrence of painful symptoms results from factors other than trabecular osteopenia. These observations thus lead one to question the utility of active medical treatment with vitamin D and/or phosphate in asymptomatic adults with VDRR.
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PMID:Bone histomorphometry in asymptomatic adults with hereditary hypophosphatemic vitamin D-resistant osteomalacia. 630 50

Proper serum phosphate concentrations are maintained by a complex and poorly understood process. Identification of genes responsible for inherited disorders involving disturbances in phosphate homeostasis may provide insight into the pathways that regulate phosphate balance. Several hereditary disorders of isolated phosphate wasting have been described, including X-linked hypophosphataemic rickets (XLH), hypophosphataemic bone disease (HBD), hereditary hypophosphataemic rickets with hypercalciuria (HHRH) and autosomal dominant hypophosphataemic rickets (ADHR). Inactivating mutations of the gene PHEX, encoding a member of the neutral endopeptidase family of proteins, are responsible for XLH (refs 6,7). ADHR (MIM 193100) is characterized by low serum phosphorus concentrations, rickets, osteomalacia, lower extremity deformities, short stature, bone pain and dental abscesses. Here we describe a positional cloning approach used to identify the ADHR gene which included the annotation of 37 genes within 4 Mb of genomic sequence. We identified missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23. These mutations in patients with ADHR represent the first mutations found in a human FGF gene.
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PMID:Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. 1106 77

Hypophosphatemic rickets, a rare metabolic bone disease, presents mainly in children but has also been reported in several adults. In this report, we describe the case of a man presenting with hip pain and weakness, both of several months' duration, and tested for hypophosphatemic rickets. The patient was eventually referred to a tertiary-care center, where he was diagnosed with bilateral subtrochanteric femoral stress fractures and severe osteopenia secondary to hypophosphatemic osteomalacia. The patient was treated with closed reduction and internal fixation and vitamin D and phosphorus. Outcomes were good at 7-month follow-up.
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PMID:Hip pain in a case of hypophosphatemic osteomalacia. 1456 Aug 28

X-linked hypophosphatemic rickets (XLH) in humans is caused by mutation in the PHEX gene. Previously, three mutations in the mouse Phex gene have been reported: Phex(Hyp), Gy, and Phex(Ska1). Here we report analysis of two new spontaneous mutation in the mouse Phex gene, Phex(Hyp-2J) and Phex(Hyp-Duk). Phex(Hyp-2J) and Phex(Hyp-Duk) involve intragenic deletions of at least 7.3 kb containing exon 15, and 30 kb containing exons 13 and 14, respectively. Both mutations cause similar phenotypes in males, including shortened hind legs and tail, a shortened square trunk, hypophosphatemia, hypocalcemia, and rachitic bone disease. In addition, mice carrying the Phex(Hyp-Duk) mutation exhibit background-dependent variable expression of deafness, circling behavior, and cranial dysmorphology, demonstrating the influence of modifying genes on Phex-related phenotypes. Cochlear cross-sections from Phex(Hyp-2J)/Y and Phex(Hyp-Duk)/Y males reveal a thickening of the temporal bones surrounding the cochlea with the presence of a precipitate in the scala tympani. Evidence of the degeneration of the organ of Corti and spiral ganglion also are present in the hearing-impaired Phex(Hyp-Duk)/Y mice, but not in the normal-hearing Phex(Hyp-2J)/Y mice. Analysis of the phenotypes noted in Phex(Hyp-Duk)/Y and Phex(Hyp-2J)/Y males, together with those noted in Phex(Ska1)/Y and Phex(Hyp)/Y males, now allow XLH-related phenotypes to be separated from non-XLH-related phenotypes, such as those noted in Gy/Y males. Also, identification of the genetic modifiers of hearing and craniofacial dysmorphology in Phex(Hyp-Duk)/Y mice could provide insight into the phenotypic variation of XLH in humans.
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PMID:New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice. 1502 77

Ultrasonographic resolution of nephrocalcinosis (NC) has been reported in children with furosemide-induced NC, but not in other entities. We report the cases of four children with metabolic bone disease, two with hypophosphatasia and two with X-linked hypophosphatemic rickets, in whom we observed resolution of renal calcifications. At the time of ultrasonographic resolution of NC, 3 of the patients were on anticalciuric diuretics, and all 4 had normal urinalysis, serum creatinine and electrolyte profiles, as well as estimated creatinine clearance. In 3 of the children, evidence of mild tubular dysfunction was found. It thus seems that in some children with bone and mineral disorders who develop NC, ultrasonographic resolution of the renal calcifications can be seen; however, mild tubular dysfunction may remain and require follow-up. Further studies are suggested to explore the possible role of anticalciuric diuretics in promoting the resolution of NC.
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PMID:Resolution of medullary nephrocalcinosis in children with metabolic bone disorders. 1597 29


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