Intestinal Phosphate Transport in Familial Hypophosphatemic Rickets

Glorieux, Francis H.; Morin, Claude; Travers, Rose; Delvin, Edgard; Poirier, R

doi:10.1203/00006450-197607000-00012

Cited by 27 publications

(12 citation statements)

References 8 publications

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“…Moreover, the exit of phosphate across the renal basolateral membrane in the Hyp mice has not been determined. Furthermore, the studies on the jejunal phosphate transport across the brush border membrane are in apparent conflict (5)(6)(7)(8), and the study of the exit of phosphate across the jejunal basolateral membrane in the Hyp mice has not been undertaken.…”

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confidence: 97%

Transport of Phosphate by Plasma Membranes of the Jejunum and Kidney of the Mouse Model of Hypophosphatemic Vitamin D-Resistant Rickets

Nakagawa

1993

Experimental Biology and Medicine

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The hypophosphatemic mouse is a useful model for the study of hypophosphatemic vitamin D-resistant rickets in humans. Hypophosphatemia and hyperphosphaturia are the main biochemical findings in the patients and in mice with the disorder. The exact membrane localization of the site of the defect in phosphate transport in humans is not known. We utilized a well-validated technique of brush border and basolateral membrane vesicles to investigate phosphate transport across the enterocyte and the renal tubule cells of the hypophosphatemic (Hyp) mice model. Phosphate uptake by brush border membranes of jejunal enterocytes revealed similar initial rates (slopes were 0.007 and 0.006 for Hyp and control mice, respectively). Kinetics of jejunal Na(+)-dependent phosphate uptake showed a Vmax of 0.21 +/- 0.03 and 0.19 +/- 0.02 nmol/mg protein/15 sec, and Km of 0.12 +/- 0.07 and 0.09 +/- 0.02 mM in the Hyp and control mice, respectively. Kinetics of basolateral uptake of phosphate were also similar (Vmax of 0.05 +/- 0.01 and 0.06 +/- 0.02 nmol/mg protein/10 sec and Km of 0.013 +/- 0.004 and 0.028 +/- 0.022 mM, respectively). On the other hand, kinetics of Na(+)-dependent phosphate uptake by renal brush border membrane vesicles (BBMV) were markedly decreased (Vmax of 0.42 +/- 0.03 and 1.09 +/- 0.06 nmol/mg protein/15 sec, P < 0.01, and Km of 0.01 +/- 0.003 and 0.05 +/- 0.02 mM, P < 0.02, in the Hyp and control mice, respectively). Kinetics of Na(+)-dependent phosphate uptake by renal basolateral membrane were not decreased (Vmax of 0.19 +/- 0.02 and 0.21 +/- 0.02 nmol/mg protein/10 sec and Km of 0.012 +/- 0.003 and 0.012 +/- 0.004 mM for Hyp and control mice, respectively). To determine whether the decrease in renal BBMV is secondary to alteration in the Na(+)-dependent phosphate transporter or due to changes in the Na+ gradient, two studies were conducted: first, a tracer exchange study in renal BBMV which showed a decrease in phosphate uptake in Hyp BBMV compared with controls, confirming the kinetic studies; and second, an Na+ permeability study in renal BBMV of Hyp and control mice which showed no differences in Na+ permeability across the renal BBMV. These findings suggest that the defect in the hypophosphatemic mice is localized only to the brush border membranes of the kidney and is not due to alteration in the driving forces across the membranes.

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confidence: 97%

Transport of Phosphate by Plasma Membranes of the Jejunum and Kidney of the Mouse Model of Hypophosphatemic Vitamin D-Resistant Rickets

Nakagawa

1993

Experimental Biology and Medicine

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“…These findings suggest that Peri.Ot.Olysis represents a more advanced stage of demineralization than does Ot.Olysis. The phenomenon of hypomineralized periosteocytic lesions (HPL) has been previously described in bone biopsies of patients with X‐linked hypophosphatemia in whom serum calcium levels are normal …”

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confidence: 99%

Calcium Deficiency Rickets in African Adolescents: Cortical Bone Histomorphometry

Schnitzler

Pettifor

2019

JBMR Plus

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Rickets due to dietary calcium deficiency has been well described in black African children, but less is known about this condition in black adolescents. We investigated 26 black adolescents (19 males aged 11 to 19 years and 7 females aged 12 to 15 years) with rachitic leg deformities and 20 controls by routine iliac crest undecalcified cortical bone histomorphometry for disturbances of bone turnover and for mineralization defects, including severity of osteocytic osteolysis (Ot.Olysis) and periosteocytic osteolysis (Peri.Ot.Olysis) of the lacunar‐canalicular space. Serum levels of calcium (sCa), 25‐hydroxyvitamin D (25OHD), 1,25‐dihydroxyvitamin D (1,25(OH) 2 D), and total alkaline phosphatase (ALP) were measured. Histomorphometry showed varying degrees of severity of secondary hyperparathyroidism (2 0 HPT) characterized by hyperosteoidosis, increased erosion, and porosis. Because osteoid was neither being mineralized nor eroded (osteoclasts cannot erode osteoid), it increasingly blocked bone surface needed for osteoclastic resorption. Where osteoid covered >50% of bone surface, osteoid thickness, severity of Ot.Olysis, and extent of Peri.Ot.Olysis increased, sCa and 25OHD declined, and 1,25(OH) 2 D and ALP increased. At 80% osteoid cover, bone remodeling had all but ceased, secondary HPT had changed to osteomalacia, and serum biochemical results had deteriorated further. Disease severity was greater in males than in females, likely because males grow faster and for longer than females. In conclusion, this cross‐sectional clinical case study presents cortical bone histomorphometric data of secondary HPT and its transition to osteomalacia in black adolescents with rickets attributable to dietary calcium deficiency. The bone disease was most severe in older adolescent males. Importantly, bone pathology of calcium deficiency rickets in adolescents was not confined to bone surfaces but also manifested at osteocyte level as Ot.Olysis and Peri.Ot.Olysis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…HR includes hereditary hypophosphatemic rickets with hypercalciuria, X-linked hypophosphatemic rickets (XLHR, 1 in 20,000 births), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR).Familial Hypophosphatemic Rickets (FHR) was found for the first time by Albright in 1937 and is also called vitamin D-resistant rickets 4-6 . It is a disease that can occur through x-linked dominant, autosomal dominant, autosomal recessive and sporadic inheritance [4][5][6][7] . Albright found that most FHR is an x-linked dominant type 7 .…”

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“…The sporadic type can easily be distinguished from the other two. In the family pedigree, there is no other FHR patient besides the patient himself 6,7 . The case that we are about to report was an X-linked dominant type of FHR.…”

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Familial Hypophosphatemic Rickets: A Case Report and Review of the Literature

Zaman,

Sarker,

Ahmed

et al. 2024

Bangabandhu Sheikh Mujib Medical Coll J

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Among the genetic disorders causing rickets because of hypophosphatemia, X- X-linked dominant hypophosphatemic rickets (XLH) is the most common, with a prevalence of 1/20,000. The defective gene is on the X chromosome, but female carriers are affected, so it is an X-linked dominant disorder. XLH associated with short stature during childhood are mostly referred to the hospital & diagnosed as vit-D deficiency rickets & received vit D before adulthood. We presented a 2-year-old boy with the complaint of walking difficulties since his 1 year of age. The patient was assessed for sociodemographic, hematological & biochemical parameters. All imaging, Laboratory parameters and positive family history confirmed the diagnosis of XLH. We treated the patient with Di basic sodium phosphate solution and 1, 25 vit D. XLH needs a good assessment, care and follow-up through a complementary medical team. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):52-55

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Intestinal Phosphate Transport in Familial Hypophosphatemic Rickets

Cited by 27 publications

References 8 publications

Transport of Phosphate by Plasma Membranes of the Jejunum and Kidney of the Mouse Model of Hypophosphatemic Vitamin D-Resistant Rickets

Transport of Phosphate by Plasma Membranes of the Jejunum and Kidney of the Mouse Model of Hypophosphatemic Vitamin D-Resistant Rickets

Calcium Deficiency Rickets in African Adolescents: Cortical Bone Histomorphometry

Familial Hypophosphatemic Rickets: A Case Report and Review of the Literature

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