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)

An unusual metabolic bone disease which developed in 11 adults receiving total parenteral nutrition (TPN) for more than 3 months was characterised by the insidious onset of bone pain which became very severe and caused considerable disability. Serum levels of calcium, phosphorus, 25-hydroxy-vitamin D, and serum immunoreactive parathyroid hormone were normal. Patchy osteomalacia with impaired mineralisation and decreased bone turnover were seen on histomorphometric analysis of bone biopsy specimens. All patients receiving long-term TPN had hypercalciuria, but no biochemical features that distinguished patients with symptoms from those without. Skeletal symptoms generally resolved 1-2 months after stoppage of the TPN infusions, despite nutritional deterioration. The pathogenesis of this syndrome remains unknown.
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PMID:Bone disease associated with total parenteral nutrition. 610 76

We report the long-term effects of dichloromethylene diphosphonate (CI2MDP), an inhibitor of bone resorption, on the skeletal lesions in multiple myeloma. Thirteen patients received either CI2MDP 1600 mg/d (seven patients) or a placebo (six patients) in addition to other chemotherapy, and the effects of treatment were followed over a period of up to 18 months in a double-blind study. CI2MDP treatment resulted in a marked reduction in bone pain, with no progression of radiologic skeletal lesions during the first year. This contrasted with a clinical deterioration and the occurrence of new fractures in half of the patients receiving the placebo. Two patients with hypercalciuria and increased excretion of hydroxyproline before treatment had normalized values following CI2MDP. Finally, iliac crest bone biopsies showed a reduction in osteoclast number after CI2MDP administration. We conclude from these results that CI2MDP could be of use in preventing the bone loss that occurs in multiple myeloma.
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PMID:Long-term effects of dichloromethylene diphosphonate (CI2MDP) on skeletal lesions in multiple myeloma. 621 70

Ten women with skeletal metastases from breast carcinoma received dichloromethylene diphosphonate (Cl2MDP), an inhibitor of osteoclast function, in a placebo-controlled, double-blind, crossover study. Eight of these patients had either hypercalcemia or hypercalciuria, and all 10 had elevated urinary hydroxyproline levels as evidence of active skeletal disease. Eight patients had moderate to severe bone pain. After eight weeks of oral dichloromethylene diphosphonate treatment (3,200 mg per day), either preceded by or followed by an eight-week placebo period, seven of eight patients with hypercalciuria had significant reductions in urinary calcium levels, and nine of 10 had reductions in urinary hydroxyproline levels (significant in eight) when the dichloromethylene diphosphonate treatment periods were compared with prestudy or placebo periods. Additionally, seven of eight subjects had decreased pain with dichloromethylene diphosphonate. There were no adverse effects other than transient diarrhea in some patients. We conclude that oral dichloromethylene diphosphonate can significantly inhibit osteoclast-mediated bone destruction in patients with bone metastases from breast cancer.
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PMID:Effects of dichloromethylene diphosphonate in women with breast carcinoma metastatic to the skeleton. 621 77

A 60-year-old woman was evaluated for bone pain and incapacitating weakness. Initial laboratory studies showed a serum calcium level of 10.1 mg/dL, severe hypophosphatemia (1.1 mg/dL), and an elevated alkaline phosphatase level. X-ray films showed changes consistent with osteomalacia. Further studies revealed hypercalciuria (448 mg/24 hr) but absent urinary phosphorus. These data indicated phosphate malabsorption. Excessive use of an aluminum hydroxide-containing antacid was the cause of this patient's failure to absorb dietary phosphate. The features of this syndrome are reviewed to increase physicians' awareness of this illness, which occurs particularly in the elderly and is easily treated.
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PMID:Osteomalacia and weakness from excessive antacid ingestion. 743 92

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

This study reports the benefits and side effects of conventional treatment, phosphate and calcitriol supplementation in patients with heritable hypophosphatemic rickets and a long-term follow-up, median of 60.9 months. The group is composed of 17 patients (ten girls). Sixteen patients presented with bone pain and/or deformities, and in one patient the diagnosis was radiological. All the patients had increased alkaline phosphatase, hypophosphatemia, decreased fractional phosphate tubular reabsorption (TRP) and maximum tubular phosphate reabsorption/glomerular filtration rate ratio (TPO4/GFR). Ten of 17 patients had metabolic acidosis, which was corrected only with the conventional treatment. Potassium citrate was prescribed to the patients who developed hypercalciuria. Excluding one patient with pulmonary dysfunction, the remaining 16 patients were divided into two groups according to the age at treatment onset (T0): group I (GI) > or =4 years (n =9) and GII <4 years (n =7). GI and GII had similar follow-up periods and treatment protocols. Seven out of nine GI patients underwent orthopedic surgery, in contrast to none of GII. Anthropometric data results showed that within each group there is no difference in weight and stature z -score at T0 and at the end of the observation (Tf), but, when both groups are compared, GII shows higher z-score for stature at T0 (p <0.05) and at Tf (p <0.05). Nephrocalcinosis developed in three cases and correlated with hypercalciuria (p <0.001) and dose of calcitriol (p =0.03). In conclusion, higher stature z-score is associated with early treatment. A careful protocol is recommended to detect such complications as nephrocalcinosis. We suggest potassium citrate for patients with hypercalciuria to avoid calcium precipitation.
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PMID:Hypophosphatemic rickets: results of a long-term follow-up. 1625 97

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of autosomal recessive inheritance that was first described in a large consanguineous Bedouin kindred. HHRH is characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histological evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. We performed a genomewide linkage scan combined with homozygosity mapping, using genomic DNA from a large consanguineous Bedouin kindred that included 10 patients who received the diagnosis of HHRH. The disease mapped to a 1.6-Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaP(i)-IIc. Nucleotide sequence analysis revealed a homozygous single-nucleotide deletion (c.228delC) in this candidate gene in all individuals affected by HHRH. This mutation is predicted to truncate the NaP(i)-IIc protein in the first membrane-spanning domain and thus likely results in a complete loss of function of this protein in individuals homozygous for c.228delC. In addition, compound heterozygous missense and deletion mutations were found in three additional unrelated HHRH kindreds, which supports the conclusion that this disease is caused by SLC34A3 mutations affecting both alleles. Individuals of the investigated kindreds who were heterozygous for a SLC34A3 mutation frequently showed hypercalciuria, often in association with mild hypophosphatemia and/or elevations in 1,25-dihydroxyvitamin D levels. We conclude that NaP(i)-IIc has a key role in the regulation of phosphate homeostasis.
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PMID:SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. 1635 14

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by mutations in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. Despite increased urinary calcium excretion, HHRH is typically not associated with kidney stones prior to treatment. However, here we describe two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation. The index patient, II-4, presented with short stature, bone pain, and knee X-rays suggestive of mild rickets at age 8.5 years. Laboratory evaluation showed hypophosphatemia, elevated 1,25(OH) (2) vitamin D levels, and hypercalciuria, later also developing vitamin D deficiency. Her sister, II-6, had a low normal serum phosphorous level, biochemically vitamin D deficiency and no evidence for osteomalacia, but had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi. Nucleotide sequence analysis of DNA from II-4 and II-6 revealed a homozygous missense mutation c.586G>A (p.G196R) in SLC34A3/NaPi-IIc. Ultrasonographic examinations prior to treatment showed grade I nephrocalcinosis for II-4, while II-6 had grade I-II nephrocalcinosis in her remaining kidney. Four siblings and the mother were heterozygous carriers of the mutation, but showed no biochemical abnormalities. With oral phosphate supplements, hypophosphatemia and hypercalciuria improved in both homozygous individuals. Renal calcifications that are presumably due to increased urinary calcium excretion can be the presenting finding in homozygous carriers of G196R in SLC34A3/NaPi-IIc, and some or all laboratory features of HHRH may be masked by vitamin D deficiency.
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PMID:Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/NaPi-IIc can be masked by vitamin D deficiency and can be associated with renal calcifications. 1852 28

Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria.
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PMID:Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report. 2007 41

Osteoporosis, a skeletal disorder characterized by a reduction in bone strength, is becoming a major public health problem in the People's Republic of China, with a rapid increase observed among the population. Chinese guidelines particularly recommend use of active vitamin D in managing osteoporosis. 1,25-(OH)2D3 (calcitriol) is an active vitamin D metabolite. It plays a role in many biological processes, especially in bone metabolism and muscle function, and is mediated by vitamin D receptors. Osteoporosis in elderly men and women is characterized by uncoupled bone remodeling, which is induced by sex hormone deficiencies, somatopause, vitamin D deficiency, reduced synthesis of D hormone, and lack of receptors or receptor affinity for D hormone in target organs. Reviewed here are six randomized controlled trials on calcitriol monotherapy and five on calcitriol therapy combined with other antiosteoporotic agents. Evidence from these trials shows that calcitriol monotherapy can improve bone mineral density in elderly osteoporotic Chinese patients but may be insufficient for long-term treatment. Calcitriol can also decrease bone turnover markers and bring about significant improvements in muscle strength. Further, calcitriol in combination with other therapeutic bone agents was shown to be well tolerated and capable of additional bone-preserving effects compared with use of calcitriol alone in areas including bone mineral density, bone turnover markers, bone pain improvement, and fracture incidence. Hypercalcemia and hypercalciuria, the most common side effects of calcitriol therapy, were not documented in the trials reviewed, and might have been the result of the low dosages used. One study showed that treatment with calcitriol can improve quality of life in patients with osteoporosis, although not to the same extent as bisphosphonates.
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PMID:Management of osteoporosis with calcitriol in elderly Chinese patients: a systematic review. 2472 92


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