X-linked hypophosphatemic rickets without ?rickets?

Econs, Michael J.; Feussner, John R.; Samsa, Gregory P.; Effman, Eric L.; Vogler, James B.; Martinez, Salutario; Friedman, Nancy; Quarles, L. Darryl; Drezner, Marc K.

doi:10.1007/bf00193821

Cited by 27 publications

(5 citation statements)

References 9 publications

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“…A similar biochemical phenotype exists in patients with X-linked hypophosphatemic rickets (XLH) and the animal model, the Hyp mouse (32,33,36,37,93,94). Several investigators have shown the presence of circulating factors in the serum of Hyp mice that inhibit sodium-dependent phosphate transport in the kidney (74,75,87).…”

Section: Biochemical Similarity Among Patients With Tumor-induced Ostmentioning

confidence: 85%

The phosphatonins and the regulation of phosphorus homeostasis

Berndt¹,

Kumar²

2005

IBMS BoneKEy

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Phosphate ions are critical for normal bone mineralization, and phosphate plays a vital role in a number of other biological processes such as signal transduction, nucleotide metabolism, and enzyme regulation. The study of rare disorders associated with renal phosphate wasting has resulted in the discovery of a number of proteins [fibroblast growth factor 23 (FGF-23), secreted frizzled related protein 4 (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF 7 (FGF-7)] that decrease renal sodiumdependent phosphate transport in vivo and in vitro. The "phosphatonins," FGF-23 and sFRP-4, also inhibit the synthesis of 1␣,25-dihydroxyvitamin D, leading to decreased intestinal phosphate absorption and further reduction in phosphate retention by the organism. In this review, we discuss the biological properties of these proteins, alterations in their concentrations in various clinical disorders, and their possible physiological role.

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Section: Biochemical Similarity Among Patients With Tumor-induced Ostmentioning

confidence: 85%

The phosphatonins and the regulation of phosphorus homeostasis

Berndt¹,

Kumar²

2005

IBMS BoneKEy

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“…Many drugs may contribute to hypophosphataemia, accounting for up to 82% of inpatient cases [29] . Furthermore, treatments for hyperphosphataemia, such as PO 4 ≡ binders or hemodialysis, may also cause this Autosomal recessive forms of FGF23-mediated hypophosphataemia are much less commonly encountered and include inactivating mutations of dentin matrix protein 1 (DMP1) (see , gene family with sequence similarity 20, member C (FAM20C), and ectonucleotide pyrophosphatase/phosphodiesterase1 (ENPP1) [33][34][35][36] (see . Patients with a DMP1 mutation are phenotypically similar to those with XLH.…”

Section: Pathophysiology/causes Of Hypophosphataemiamentioning

confidence: 99%

A Practical Clinical Approach to Paediatric Phosphate Disorders

Imel¹,

Carpenter

2015

Calcium and Bone Disorders in Children and Adolescents

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Phosphate metabolism is critical to multiple systems and cellular functions. Disruption of any point in the pathways of phosphate metabolism may cause serum phosphate abnormalities and resultant acute or chronic clinical conditions. The study of phosphate disorders has revealed a wealth of information regarding normal phosphate physiology. Careful evaluation of affected patients based on pathophysiologic assessments will usually identify the aetiology of hypophosphataemia or hyperphosphataemia, which is important to guide appropriate therapy. Because of the relative importance of chronic hypophosphataemia and hyperphosphataemia to bone disease, much of this chapter will focus on chronic disorders, especially those mediated by excess or deficient fibroblast growth factor 23 functioning.

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“…Biochemically, the disorder is characterized by hypophosphatemia as a result of renal phosphate wasting and inappropriately low or normal calcitriol concentrations. Radiographic evidence for rickets is common in children, although not universally present (36), and osteomalacia is seen on bone biopsy.…”

Section: Xlhmentioning

confidence: 99%

Fibroblast Growth Factor 23

Imel¹,

Econs²

2005

Journal of the American Society of Nephrology

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A lthough phosphate is important in skeletal mineralization, energy metabolism, and multiple enzymatic processes, little has been understood about the regulation of phosphate in health and disease until recently. Genetic and acquired disorders of phosphate homeostasis have begun to reveal important mechanisms for the regulation of phosphate metabolism. Candidate phosphate-regulating hormones ("phosphatonins") have been discovered, and their actions and interactions continue to be elucidated in an exciting area of ongoing clinical and basic research. Autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), tumor-induced osteomalacia (TIO), and fibrous dysplasia (FD) have similar phenotypes of hypophosphatemia, urinary phosphate wasting as measured by a low tubular maximum reabsorption of phosphate per deciliter of glomerular filtrate (TmP/GFR), osteomalacia, and rickets. The phenotypic similarities suggest a common metabolic pathophysiology. In addition, recent evidence concerning tumoral calcinosis, which results in hyperphosphatemia, inappropriately elevated calcitriol concentrations, and soft tissue calcifications and can be considered the phenotypic "converse" of the phosphate wasting disorders, indicates that this disorder may result from perturbations of some of the same metabolic pathways. Fibroblast growth factor 23 (FGF23) is a recently discovered, novel, secreted protein hormone involved in the pathogenesis of these disorders. This review focuses on the relationship of FGF23 to various disorders of phosphate homeostasis and its potential regulation and function in normal physiology. Hypophosphatemic DisordersADHR ADHR, initially described by Bianchine et al. (1), is characterized by renal phosphate wasting, hypophosphatemia, low or inappropriately normal calcitriol concentrations, and osteomalacia. Econs and McEnery (2) described a large ADHR kindred. Affected patients presented either in childhood with hypophosphatemia and rickets, which resulted in lower extremity deformities, or after puberty with hypophosphatemic osteomalacia, manifesting in weakness, fatigue, bone pain, and fractures. Patients with adult onset of symptoms clinically resemble TIO, but the disease is not a paraneoplastic process. To date, delayed onset of clinically evident disease has been observed only in female individuals. ADHR also exhibits incomplete penetrance, and, in some cases, the clinical and biochemical phenotype spontaneously resolved in patients who were previously documented to have hypophosphatemic rickets (2).The ADHR consortium used the positional cloning approach to identify the gene responsible for ADHR, FGF23 (3). ADHR results from mutations in either arginine 176 or arginine 179 in FGF23. These arginines make up an RXXR cleavage site, and mutations in either of these arginines protect the protein from degradation, potentially increasing the circulating concentration of FGF23 and, thereby, leading to the disease phenotype (4 -6). FGF23 is a 251-amino acid protein in the FGF fa...

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X-linked hypophosphatemic rickets without ?rickets?

Cited by 27 publications

References 9 publications

The phosphatonins and the regulation of phosphorus homeostasis

The phosphatonins and the regulation of phosphorus homeostasis

A Practical Clinical Approach to Paediatric Phosphate Disorders

Fibroblast Growth Factor 23

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