Hereditary hypophosphatemic rickets and tumor-induced osteomalacia
- Steven J Scheinman, MD
Steven J Scheinman, MD
- President and Dean
- The Commonwealth Medical College
- Marc K Drezner, MD
Marc K Drezner, MD
- Section Editor — Bone Disease
- Professor of Medicine
- University of Wisconsin Medical School
- Section Editors
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor Emeritus
- University of Rochester School of Medicine and Dentistry
- Mitchell E Geffner, MD
Mitchell E Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
The term vitamin D-resistant rickets (VDRR) originally was used to describe a syndrome of hypophosphatemia and rickets (and/or osteomalacia) that resembled vitamin D deficiency but did not respond to vitamin D replacement or pharmacologic doses of vitamin D. Most of these cases were caused by renal phosphate wasting, leading to the alternate name of "phosphate diabetes." This disorder is now called hereditary hypophosphatemic rickets because the primary problem is now recognized to be phosphate wasting rather than true vitamin D resistance.
By contrast, true vitamin D resistance is characterized by hypocalcemia as well as hypophosphatemia and results from an inherited defect in the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D or in the calcitriol receptor that limits the interaction with 1,25-dihydroxyvitamin D. (See "Etiology and treatment of calcipenic rickets in children", section on 'Hereditary resistance to vitamin D' and "Etiology and treatment of calcipenic rickets in children", section on '1-alpha-hydroxylase deficiency'.)
Hereditary forms of hypophosphatemia or hypophosphatemic rickets include X-linked, autosomal dominant and autosomal recessive disease, as well as hypophosphatemic rickets with hypercalciuria. The X-linked form is most common; the other forms are rare, with fewer than 100 reported cases. An acquired disorder, tumor-induced (or oncogenic) osteomalacia, has similar clinical manifestations to the familial syndromes. In addition to hypophosphatemia, these disorders all have normal serum levels of calcium and parathyroid hormone. Most of these disorders also have high circulating levels of fibroblast growth factor 23 (FGF23), a circulating hormone that causes renal phosphate wasting and is a common final pathway (figure 1).
The etiology and treatment of hereditary hypophosphatemic rickets and tumor-induced osteomalacia will be reviewed here. The clinical manifestations and evaluation of rickets and osteomalacia are discussed separately. (See "Overview of rickets in children" and "Epidemiology and etiology of osteomalacia".)
X-linked hypophosphatemia (XLH) is a dominant disorder with a prevalence of approximately one case per 20,000 live births .
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- Clinical features
- - Children
- - Adults
- - Complications
- - Adjuvant therapy
- AUTOSOMAL DOMINANT
- Clinical findings
- AUTOSOMAL RECESSIVE
- HYPOPHOSPHATEMIA WITH HYPERCALCIURIA
- Hypophosphatemic rickets with hypercalciuria
- - Pathogenesis
- - Clinical features
- - Treatment
- Dent's disease
- Idiopathic hypercalciuria
- TUMOR-INDUCED OSTEOMALACIA
- Clinical features
- SUMMARY AND RECOMMENDATIONS