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Hereditary hypophosphatemic rickets and tumor-induced osteomalacia

Steven J Scheinman, MD
Marc K Drezner, MD
Section Editors
Richard H Sterns, MD
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD


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 diseases, 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 (PTH). 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 [1].

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Literature review current through: Dec 2017. | This topic last updated: Sep 26, 2017.
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