X-linked hypophosphataemia and autosomal recessive vitamin D dependency: Models for the resolution of vitamin D refractory rickets

Scriver, Charles R.; Glorieux, Francis H.; Reade, T; Tenenhouse, Harriet S.

doi:10.1007/978-94-011-6159-6_11

Cited by 7 publications

(6 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, phosphate supplements increase the overall body growth of the Hyp mice [3]. Humans with this disease also show a beneficial response to oral phosphate supplements [19]. The Hyp mice have low magnesium levels of the ash of both the femur and incisor.…”

Section: Discussionmentioning

confidence: 98%

Osteomalacia and altered magnesium metabolism in the X-linked hypophosphatemic mouse

1979

View full text Add to dashboard Cite

Summary.A new genetic mutant in mice, Hyp, has been proposed as a model for the human disease Xlinked hypophosphatemia (the most common form of vitamin D-resistant rickets). The gene is Xlinked, dominant, and produces reduced renal tubular reabsorption of phosphate, hypophosphatemia, and dwarfism. Our goal was to evaluate the skeletal changes histologically and to measure chemically the prominant blood and bone minerals to judge the suitability of this mutant as a model for the human disease. Thirteen-week-old hemizygous Hyp male mice were compared with their normal lfttermate controls. The Hyp mice were hypocalcemic, hypophosphatemic, hypermagnesemic, and had elevated plasma alkaline phosphatase. The femur ash weighed less than half the normal ash weight but had a normal Ca:P ratio. The ash composition was high in %Na and K but low in %Mg. The mandibular incisor ash was also low in %Mg. Histologically the femur showed wide osteoid borders and wide epiphyseal plate. Microradiography revealed reduced bone density and enlarged osteocyte lacunae. Skeletal muscle samples, although smaller in the Hyp mice, showed no striking alternations in inorganic or total phosphate content, dry weight (as % wet weight), or extracellular fluid space. The Hyp gene in mice seems to produce a condition similar to that of X-linked hypophosphatemia in humans.Send offprint requests to Ralph A. Meyer, Jr., at the above address.

show abstract

Section: Discussionmentioning

confidence: 98%

Osteomalacia and altered magnesium metabolism in the X-linked hypophosphatemic mouse

1979

View full text Add to dashboard Cite

show abstract

“…In eight patients with this syndrome, low concentrations of 1,25-dihydroxyvitamin D [1, were found in plasma (2), and physiological doses of 1,25(OH)2D3 have caused remission in at least five patients (3)(4)(5)(6). Vitamin D dependency, in these patients, would seem to result from deficient renal 25-hydroxyvitamin D (25OHD) la-hydroxylase activity.…”

mentioning

confidence: 95%

A Familial Syndrome of Decrease in Sensitivity to 1,25-Dihydroxyvitamin D*

Marx

Spiegel

Brown

et al. 1978

The Journal of Clinical Endocrinology & Metabolism

134

View full text Add to dashboard Cite

Typical features of hereditary vitamin D-dependent (pseudovitamin D-deficient) rickets were observed beginning at ages 20 and 5 months in a brother and sister. Both had calcium malabsorption correctable with high doses of 25-hydroxyvitamin D. During periods of hypocalcemia they both manifested secondary hyperparathyroidism with hypophosphatemia and high serum concentrations of endogenously produced 1,25-dihydroxyvitamin D. In each, normalization of serum calcium concentration and resolution of osteomalacia were obtained with continuous administration of high doses of ergocalciferol or high doses of 1,25-dihydroxycholecalciferol. Chemical features of vitamin D deficiency were corrected in the presence of high circulating concentrations of 1,25-dihydroxyvitamin D2, produced endogenously, or of 1,25-dihydroxyvitamin D3, administered by mouth. Serum concentrations of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal in five first degree relatives. We conclude that in these five first degree relatives. We conclude that in these siblings, rickets and osteomalacia resulted from a hereditary decreased sensitivity to 1,25-dihydroxyvitamin D at the intestine and perhaps other vitamin D target tissues.

show abstract

“…One patient with this disease was found to have a milk phosphate content of half the normal value [4,5]. Since two-thirds of the phosphate in milk is protein-bound [21], the low phosphate level in this patient suggests an alteration in her milk protein level as well.…”

Section: Discussionmentioning

confidence: 98%

“…Her milk had 54 mg/liter of phosphorus, which was half the normal value [6]. This was judged inadequate to support the normal development of the child [4,5]. In the absence of data from other afflicted humans, it is not known how common altered milk composition is in this disease.…”

mentioning

confidence: 98%

See 1 more Smart Citation

Normal milk composition in lactating X-linked hypophosphatemic mice despite continued hypophosphatemia

Delzer

Meyer

1983

Calcif Tissue Int

View full text Add to dashboard Cite

Patients with X-linked hypophosphatemia and mice bearing the Hyp gene have reduced renal tubular reabsorption of phosphate and an osteomalacic bone disease. To test if altered phosphate transport also exists in the mammary glands, milk was analyzed from normal (n = 9) and heterozygous Hyp (n = 8) mice 14 days after giving birth. Inorganic phosphate, total phosphate, calcium, magnesium, sodium, and potassium were measured; percent cream, fat, water, and nonfat organic solids were measured; and protein was measured. No significant differences (NSD) were found except for greater sodium in Hyp milk. There was also NSD in litter weight. The lactating Hyp had a lower body weight and remained hypophosphatemic relative to lactating normals, but both groups had higher plasma phosphate than nonlactating controls of the same genotype. The data suggest that Hyp mice can accumulate a normal amount of phosphate in their milk despite the plasma phosphate being two-thirds of normal. These data, with other recent reports of different organ systems, suggest that the altered phosphate transport activity may be restricted to the kidney.

show abstract

X-linked hypophosphataemia and autosomal recessive vitamin D dependency: Models for the resolution of vitamin D refractory rickets

Cited by 7 publications

References 38 publications

Osteomalacia and altered magnesium metabolism in the X-linked hypophosphatemic mouse

Osteomalacia and altered magnesium metabolism in the X-linked hypophosphatemic mouse

A Familial Syndrome of Decrease in Sensitivity to 1,25-Dihydroxyvitamin D*

Normal milk composition in lactating X-linked hypophosphatemic mice despite continued hypophosphatemia

Contact Info

Product

Resources

About