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Hypophosphatemia disorders can be divided conceptionally into those with increased fibroblast growth factor 23 (FGF23) levels (caused by mutations of extrarenal factors or by tumors) and those with normal or suppressed FGF23 (due to mutations tubular phosphate transporters). Rickets are the consequence of dysregulated phosphate transport and/or FGF23 excess.
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X-linked hypophosphatemia is due to a hemizygous dominant mutation of the phosphate-regulating endopeptidase homolog, X-linked gene leading
Hypophosphatemic Rickets
Section snippets
Key points
Phosphate homeostasis
Phosphorus, the most abundant anion in the body,7 is an essential element for numerous cellular molecules, including nucleic acids, proteins, and lipids. It is critical for bone formation, and it is involved in acid-base regulation and cellular physiology. Rickets is a disease of the growth plate due to insufficient availability of PO4 (inorganic phosphorus [Pi]). It only affects growing children.2 PO4 deficiency may be due to poor absorption from the gut or renal wasting.
The average adult body
Clinical Findings
The clinical presentation of hypophosphatemia syndromes depends on the duration of hypophosphatemia and the age of patients (infancy and childhood vs adulthood). Different forms of hypophosphatemia cause similar, albeit not identical, clinical features and radiographical changes. Bone pain and deformities, fractures, disproportionate short stature, and dental abscesses are predominantly seen in chronically hypophosphatemic children. Adults may present with osteomalacia, bone pain, stiffness,
Hypophosphatemia syndromes
From a mechanistic and conceptual viewpoint, hypophosphatemia syndromes can be divided into those with increased FGF23 levels and those with normal or suppressed FGF23. Hypophosphatemia with increased FGF23 levels is caused by extrarenal factors, whereas hypophosphatemia with normal or suppressed FGF23 is due to mutations in genes encoding tubular PO4 transporters. Rickets are the consequence of dysregulated PO4 transport. Inherited disorders of renal PO4 handling contrast with acquired
Summary
Hypophosphatemic rickets, most due to the X-linked dominant form caused by pathogenic variants of the PHEX gene, continues to pose therapeutic challenges with important consequences for growth and bone development, high risk of fractions and poor bone healing, dental problems, and nephrolithiasis or nephrocalcinosis.
Conventional treatment consists of PO4 supplement and pharmacologically dosed calcitriol carefully monitoring for clinical efficacy and treatment-emergent adverse effects. Genetic
Acknowledgments
We thank Giuseppe Pascale for help in the design of the figures.
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2022, International Journal of PaleopathologyCitation Excerpt :This last process triggers RANKL expression, causing preosteoclasts to transform into osteoclasts that dissolve the bone matrix to release calcium and phosphorus into the blood (Brickley et al., 2020, p. 93). Genetic polymorphisms affecting phosphorus regulation (hypophosphatemic rickets) (Bitzan and Goodyer, 2019), calcium-sensing receptors (CaSR) (Wu et al., 2017), or VDR function (vitamin D-resistant rickets) (Liberman, 2007) can also result in skeletal rickets. Many diseases and iatrogenic factors also affect the bioavailability, synthesis, or metabolism of vitamin D, such as hyperparathyroidism, celiac disease, cystic fibrosis, chronic kidney disease, or medications used to treat high cholesterol (Holick, 2007).
Genetic and clinical profile of patients with hypophosphatemic rickets
2022, European Journal of Medical GeneticsCitation Excerpt :Phosphate deficiency is the primary defect in phosphopenic rickets, and is chiefly caused by genetic disorders of renal phosphate handling leading to impaired tubular reabsorption. The important genetic causes of phosphopenic rickets are FGF23 related X-linked dominant, autosomal dominant and autosomal recessive hypophosphatemic rickets (Bitzan and Goodyer, 2019). Impaired proximal tubular reabsorption of phosphate is also seen in patients with Dent disease, renal Fanconi syndrome and renal tubular acidosis (RTA).
Educational Case: Rickets
2022, Academic PathologyCitation Excerpt :1,25-hydroxy-vitamin D has several systemic effects. However, 1,25-hydroxy-vitamin D acts on the kidney; nephron distal tubules respond to active vitamin D via the transient receptor potential vanilloid family (TRPV5), resulting in calcium reabsorption.20 Similarly, active vitamin D forms a heterodimeric complex with nuclear retinoid X receptor (RXR) within intestinal epithelial cells leading to the expression of TRPV6, which facilitates calcium absorption by the duodenum.19
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