Disease relevance of Hypophosphatemia

• Severe proximal myopathy associated with hypophosphatemia developed in three patients with chronic renal failure who had been treated with aluminum hydroxide gel [1].
• Intact dogs (group I) undergoing continuous intravenous PTH infusion for 12 d developed sustained hypercalcemia and hypophosphatemia, and plasma calcitriol concentration decreased from 23 +/- 3 to 14 +/- 3 pg/ml (P less than 0.01) [2].
• Targeted ablation of the vitamin D receptor (VDR) results in hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, osteomalacia, and alopecia--the last a consequence of defective anagen initiation [3].
• The decreased serum intact parathyroid hormone levels in more severe acidosis may be the consequence of hypophosphatemia and/or increased serum 1,25-(OH)2D concentrations [4].
• Recombinant human erythropoietin and hypophosphatemia in patients with cirrhosis [5].

Psychiatry related information on Hypophosphatemia

• The continuous infusion of a concentrated, high-caloric glucose solution intravenously into underfed or 3-day-starved rats at a rate of 390 kcal/kg/day results in hypophosphatemia, muscular weakness, neuropathy, lethargy, occasional convulsions, and eventual coma and death [6].
• OBJECTIVE: Hypophosphatemia is a well-known complication of the refeeding syndrome in severe cases of anorexia nervosa, described mostly as a result of refeeding with total parenteral nutrition [7].

High impact information on Hypophosphatemia

• We conclude that the subjects with hypercalciuria and the patients with HHRH shared a hereditary renal phosphate leak that led to hypophosphatemia, elevated serum concentrations of 1,25-(OH)2D, increased intestinal calcium absorption, and hypercalciuria [8].
• We propose that the pivotal defect in this syndrome is a renal phosphate leak resulting in hypophosphatemia with an appropriate elevation of 1,25-dihydroxyvitamin D levels, which causes increased calcium absorption, parathyroid suppression, and hypercalciuria [9].
• Hypophosphatemia is common in hospitalized patients and occurs under a variety of circumstances other than parathyroid hormone excess [10].
• Thus, sFRP-4 displays phosphatonin-like properties, because it is a circulating protein that promotes phosphaturia and hypophosphatemia and blunts compensatory increases in 1alpha, 25-dihydroxyvitamin D [11].
• The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)2D3 together with decreased PTH mRNA levels (25 +/- 8% of controls, P < 0.01) and serum immunoreactive PTH (4.7 +/- 0.8: 22.1 +/- 3.7 pg/ml; low phosphate: control, P < 0.05) [12].

Chemical compound and disease context of Hypophosphatemia

• These results indicate that hypophosphatemia is associated with impaired glucose metabolism in both the hyperglycemic and euglycemic states, and that this associated primarily reflects decreased tissue sensitivity to insulin [13].
• The remaining two untreated patients (aged 2 and 37 yr) displayed characteristic hypophosphatemia before calcitriol therapy [14].
• Mild hypophosphatemia was present in SH on +D (5.8 vs. 6.9 mg/dl, P less than 0.005) and -D diets (6.2 vs. 7.9 mg/dl, P less than 0.005), and was associated with higher rates of cyclic adenosine monophosphate excretion (32.8 vs. 26.9 and 48.5 vs. 41.0 nmol/mg of creatinine, respectively) [15].
• These data demonstrate that hypophosphatemia is associated with an augmented glucose-stimulated insulin release, without any effect on tolbutamide-stimulated insulin release [16].
• Complete remission of the leukemia and fibrosis was achieved with a single 3-week course of low-dose cytarabine and hydroxyurea, with resolution of the hypocalcemia and hypophosphatemia [17].

Biological context of Hypophosphatemia

• To determine which of these abnormalities is responsible for impaired chondrocyte apoptosis and subsequent rachitic changes, two additional models were examined: diet-induced hypophosphatemia/hypercalcemia and hypophosphatemia secondary to mutations in the Phex gene [18].
• Gy maps closely (crossover value 0.4-0.8%) to another X-linked gene (Hyp) that also causes hypophosphatemia in the mouse [19].
• The observation that normalization of mineral ion homeostasis in the VDR-null mice prevents rachitic changes suggests that rickets is secondary to hypocalcemia, hypophosphatemia, or hyperparathyroidism, rather than impaired VDR action [18].
• Hypocalcemia and hypophosphatemia regulate PTH gene expression post-transcriptionally [20].
• This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets [21].

Anatomical context of Hypophosphatemia

• In addition, implantation of CHO cells expressing the mutant FGF-23 protein caused hypophosphatemia and the decrease of bone mineral content [22].
• Young NHERF-1(-/-) male mice display defective targeting of Npt2a to apical membranes in the renal proximal tubule and manifest hypophosphatemia and increased urinary excretion of phosphate [23].
• Available evidence today indicates that the bone defect in XLH is caused not only by hypophosphatemia and altered vitamin D metabolism but also by factor(s) locally released by osteoblast cells (ObCs) [24].
• The X-linked Hyp mouse, a murine homologue of X-linked hypophosphatemia in humans, is characterized by rachitic bone disease, hypophosphatemia, impaired renal brush-border membrane Na(+)-phosphate cotransport and abnormal regulation of renal vitamin D metabolism [25].
• Chronic hypophosphatemia in humans is associated with a slow depletion of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) in erythrocytes, combined with shape alteration, impaired deformability, and viability of the cells [26].

Gene context of Hypophosphatemia

• At comparable circulating levels, the mutant form was more potent in inducing hypophosphatemia, in decreasing circulating concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and in causing rickets and osteomalacia in these animals compared with wild type FGF23 [27].
• These results demonstrate that MEPE elevation in Hyp mice does not contribute to the hypophosphatemia associated with inactivating Phex mutations and is therefore not phosphatonin [28].
• In summary, the Gy mutation is associated with a recessively expressed mutation of the spermine synthase gene, leading to spermine deficiency, and a dominantly expressed mutation of the Pex gene, leading to hypophosphatemia [29].
• The present results indicate that the low serum IGFBP-3 activity in Hyp mice is not related to hypophosphatemia per se [30].
• Phosphate deprivation induced hypophosphatemia IGF-II [30].

Analytical, diagnostic and therapeutic context of Hypophosphatemia

• In situ hybridization showed that hypophosphatemia decreased PTH mRNA in all the parathyroid cells [12].
• Surgical joining of normal to Hyp mice by parabiosis results in the normal mice developing low renal retention of phosphate and hypophosphatemia [31].
• Hemangiopericytoma-induced osteomalacia: tumor transplantation in nude mice causes hypophosphatemia and tumor extracts inhibit renal 25-hydroxyvitamin D 1-hydroxylase activity [32].
• Hyp mice are an animal model for the human disease X-linked hypophosphatemia [33].
• Preventing hypophosphatemia during total parenteral nutrition [34].

References