Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Renal ultrasonography was performed on 23 patients with X-linked hypophosphatemic rickets (XLH) and 11 patients with autosomal recessive vitamin D-dependent rickets (ARVDD). A pattern of increased echogenicity of the renal pyramids (ERP) was identified in 11/23 patients with XLH and 3/11 patients with ARVDD; this ultrasonographic finding has previously been associated with medullary nephrocalcinosis. Patients with XLH and ERP had significantly higher mean serum calcium and phosphate concentrations, more frequent episodes of hypercalcemia, and higher doses of oral vitamin D and phosphate during the first 3 years of therapy. Episodes of hypercalcemia were more frequent when patients received higher doses of vitamin D2 (greater than 4000 IU/kg/day) or 1,25-dihydroxycholecalciferol (greater than 40 ng/kg/day). Episodes of hypercalciuria were significantly increased at doses of greater than 20 ng/kg/day 1,25-dihydroxycholecalciferol. In patients with ARVDD, ERP was also correlated with vitamin D dose and frequency of hypercalcemia episodes. ERP was not associated with an elevation of serum creatinine or loss of urinary concentrating ability in either patient group.
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PMID:Nephrocalcinosis and its relationship to treatment of hereditary rickets. 282 87

A single case of hypophosphatemic rickets with hypercalciuria and an elevated level of serum 1,25 dihydroxyvitamin D is reported. The characteristic features (genu valgum, rickets, short stature, increased renal phosphate excretion, decreased serum phosphorus level, elevated serum alkaline phosphatase level, and normal serum calcium level) were comparable to those in hypophosphatemic vitamin D resistant rickets. Massive doses of 1 alpha-hydroxyvitamin D were not effective for the rickets and the biochemical defect in this patient. Long-term phosphate supplementation on its own resulted in the reversal of all clinical and biochemical abnormalities except for the decreased ratio between the maximum tubular reabsorption rate for phosphorus and the glomerular filtration rate. In this patient, the concentration of serum 1,25 dihydroxyvitamin D seemed to be controlled by the concentration of serum phosphorus rather than by the serum parathyroid hormone level. It is noted that this is the first case of a single hypophosphatemic rickets with hypercalciuria.
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PMID:A single case of hypophosphatemic rickets with hypercalciuria. 376 Nov 17

Although conventional therapy (pharmacologic doses of vitamin D and phosphorus supplementation) is usually successful in healing the rachitic bone lesion in patients with X-linked hypophosphatemic rickets, it does not heal the coexistent osteomalacia. Because serum 1,25-dihydroxyvitamin D levels are inappropriately low in these patients and high calcitriol concentrations may be required to heal the osteomalacia, we chose to treat five affected subjects with high doses of calcitriol (68.2 +/- 10.0 ng/kg total body weight/d) and supplemental phosphorus (1-2 g/d) performing metabolic studies and bone biopsies before and after 5-8 mo of this therapy in each individual. Of these five patients, three (aged 13, 13, and 19 yr) were receiving conventional treatment at the inception of the study and therefore showed base-line serum phosphorus concentrations within the normal range. The remaining two untreated patients (aged 2 and 37 yr) displayed characteristic hypophosphatemia before calcitriol therapy. All five patients demonstrated serum calcitriol levels in the low normal range (22.5 +/- 3.2 pg/ml), impaired renal phosphorus conservation (tubular maximum for the reabsorption of phosphate per deciliter of glomerular filtrate, 2.13 +/- 0.20 mg/dl), and osteomalacia on bone biopsy (relative osteoid volume, 14.4 +/- 1.7%; mean osteoid seam width, 27.7 +/- 3.7 micron; mineral apposition rate, 0.46 +/- 0.12 micron/d). On high doses of calcitriol, serum 1,25-dihydroxyvitamin D levels rose into the supraphysiologic range (74.1 +/- 3.8 pg/ml) with an associated increment in the serum phosphorus concentration (2.82 +/- 0.19 to 3.78 +/- 0.32 mg/dl) and improvement of the renal tubular maximum for phosphate reabsorption (3.17 +/- 0.22 mg/dl). The serum calcium rose in each patient while the immunoactive parathyroid hormone concentration measured by three different assays remained within the normal range. Most importantly, repeat bone biopsies showed that high doses of calcitriol and phosphorus supplements had reversed the mineralization defect in all patients (mineral apposition rate, 0.88 +/- 0.04 micron/d) and consequently reduced parameters of bone osteoid content to normal (relative osteoid volume, 4.1 +/- 0.7%; mean osteoid seam width, 11.0 +/- 1.0 micron). Complications (hypercalcemia and hypercalciuria) ensued in four of these five patients within 1-17 mo of documented bone healing, necessitating reduction of calcitriol doses to a mean of 1.6 +/- 0.2 micrograms/d (28 +/- 4 ng/kg ideal body weight per day). At follow-up bone biopsy, these four subjects continued to manifest normal bone mineralization dynamics (mineral apposition rate, 0.88 +/-0.10 micrometer/d) on reduced doses of 1.25-dihydroxyvitamin D with phosphorus supplements (2 g/d) for a mean of 21.3 +/- 1.3 mo after bone healing was first documented. Static histomorphometric parameters also remained normal (relative osteoid volume, 1.5 +/- 0.4%; mean osteoid seam width, 13.5 +/- 0.8 micrometer). These data indicate that administration of supraphysiologic amounts of calcitriol, in conjunction with oral phosphorus, results in complete healing of vitamin D resistant osteomalacia in patients with X-linked hypophosphatemic rickets. Although complications predictably require calcitriol dose reductions once healing is achieved, continued bone healing can be maintained for up to 1 yr with lower doses of 1,25-dihydroxyvitamin D and continued phosphorus supplementation.
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PMID:Healing of bone disease in X-linked hypophosphatemic rickets/osteomalacia. Induction and maintenance with phosphorus and calcitriol. 383 45

Treatment for X-linked hypophosphatemia (XLH; vitamin D metabolites and phosphate salts) may result in hypercalcemia, hypercalciuria, nephrocalcinosis, and hyperparathyroidism. Cardiovascular abnormalities occur in association with these complications, but have not been reported in XLH. We hypothesized that such abnormalities may occur in XLH and evaluated cardiovascular status in 13 patients with this disease. All patients were asymptomatic and had normal cardiovascular physical examinations and Holter studies. Serum calcium and creatinine clearance were normal in all. However, all patients had mild to moderate nephrocalcinosis. Left ventricular hypertrophy was diagnosed by electrocardiogram in three and by ultrasonography in seven children. Baseline blood pressure (BP) was normal (mean +/- SD, 116 +/- 15/74 +/- 6 mm Hg). During exercise stress testing, systolic BP increased in all patients, but the maximal systolic pressure was less than that in healthy age- and sex-matched controls (156 +/- 20 vs. 175 +/- 23; P = 0.002, by t test). An abnormal increase in diastolic BP occurred at all levels of work load in XLH patients; their peak exercise diastolic BP was 91 +/- 12 vs. 72 +/- 6 mm Hg in controls (P < 0.0001, by t test). Whether these abnormal findings are primary defects in XLH or represent complications of treatment is unclear. Patients with XLH should be monitored closely for the development of hypertension and left ventricular hypertrophy. Investigation of the mechanisms involved and establishment of therapeutic guidelines are indicated.
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PMID:Cardiovascular abnormalities in patients with X-linked hypophosphatemia. 925 16

To improve the growth failure, bowed legs, and biochemical and radiological abnormalities in patients with X-linked hypophosphatemic vitamin D resistant rickets (XLH), combined therapy of phosphate and calcitriol is the best therapeutic approach at present. However, the complications involving combined therapy, such as hypercalcemia, nephrocalcinosis and hyperparathyroidism, are not fully solved. To achieve better control, new therapeutic approaches have been reported recently, for example, growth hormone (GH) or new vitamin D analogs. GH improved linear growth, decreased phosphate reabsorption and increased 1-alpha-hydroxylase activity. Furthermore, 24R,25-dihydroxyvitamin D3 (24,25) improved the bone lesions in hypophosphatemic (Hyp) mice, and also in XLH, without the adverse effects such as hypercalcemia or hypercalciuria compared with 1,25-dihydroxyvitamin D3. These new approaches should be considered for the treatment of patients with XLH.
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PMID:Medical management and complications of X-linked hypophosphatemic vitamin D resistant rickets. 931 1

This report concerns an 11-year-old boy who manifested hypophosphatemic rickets associated with congenital microvillous atrophy (CMA). He had been suffering from vomiting and severe diarrhea from the first day of life and had been treated with total parenteral nutrition (TPN) since he was 67 days old. At 4 years of age, intestinal biopsy resulted in a diagnosis of CMA. He was admitted to our hospital complaining of leg pain at the age of 11. Laboratory data revealed hypophosphatemia, elevated serum 1, 25-dihydroxyvitamin D (1,25(OH)2D) levels, and hypercalciuria. A roentgenogram showed rickets in the extremities. A balance study of phosphate in urine and stool indicated that the amount of phosphate leaking into the stool was greater than that into the urine. Moreover, the total amount of phosphate leaking from both the intestine and kidney exceeded the amount of phosphate intake from TPN. The rickets was healed by increasing the phosphate concentration in TPN. This case is different from X-linked hypophosphatemic rickets but similar to hereditary hypophosphatemic rickets with hypercalciuria (HHRH) in terms of hypercalciuria and elevated serum 1,25(OH)2D levels. The effectiveness of phosphate treatments used here is also similar to that used for HHRH. However, this type of hypophosphatemic rickets is unique in that phosphate leaking into the intestine plays an important role in its pathogenesis.
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PMID:Hypophosphatemic rickets accompanying congenital microvillous atrophy. 984 14

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

Vitamin D-resistant rickets is a group of rare disease characterized by lack of reaction to vitamin D administered in doses sufficient to manage patients with rickets caused by vitamin D deficiency. These disorders result from disturbed metabolism and activity of vitamin D and/or disturbed phosphate metabolism. The most common vitamin D-resistant form of rickets is X-linked hypophosphatemic vitamin D-resistant rickets. Other forms are as the following: oncogenic hypophosphatemic osteomalacia, autosomal dominant hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria and pseudo-vitamin D deficient rickets type I and II.
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PMID:[Vitamin D-resistant rickets]. 1586 46

X-linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria, and tumor-induced osteomalacia share clinical and biochemical features, and are collectively referred to as hypophosphatemic rickets (HR). Recently, the molecular bases of HR were elucidated. A review of medical records and mutational analyses of the PHEX and FGF23 genes were performed on 17 unrelated Korean children with HR. The male-to-female ratio was 3:14, and 5 patients were familial. Initial laboratory tests revealed typical features of HR. Seven different PHEX mutations were detected in 8 patients: 2 missense mutations, 2 nonsense mutations, and 3 short deletions. No functional FGF23 mutation was detected in any patient. Patients with the PHEX mutation tended to have more severe skeletal disease than those without. Of the patients with this mutation, no genotype-phenotype correlation and no gene dosage effect were noted. Treatment with vitamin D and phosphate resulted in only a partial growth improvement in most cases, and was frequently complicated by hypercalciuria, hypercalcemia, nephrocalcinosis, or hyperparathyroidism. Renal glycosuria was detected in six cases and was associated with more severe skeletal disease. We conclude that current HR treatment is not fully safe or effective, and that close monitoring of treatment effectiveness and for complications should be performed during long-term treatment. No genotype-phenotype correlation in XLH was detected in this study, but a large-scaled study on this topic is warranted. The large proportion of patients with a normal genetic study suggests the possibility of other causative gene(s).
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PMID:A clinical and molecular genetic study of hypophosphatemic rickets in children. 1605 33


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