Idiopathic Hypercalciuria and Hereditary Hypophosphatemic Rickets

Martin Tieder, David Modai, Uri Shaked, Ruth Samuel, Raphael Arie, Aharon Halabe, Joseph Maor, Joshua Weissgarten, Zhan Averbukh, Natan Cohen, Samuel Edelstein, Uri Liberman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Among 59 closely related members of one Bedouin tribe, we identified 9 who had the characteristic features of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We found “idiopathic” hypercalciuria in 21 of the 50 asymptomatic members. The biochemical abnormalities observed in these 21 subjects were qualitatively similar to those in the 9 with HHRH, but were quantitatively milder. The urinary calcium concentration was 0.43±0.14 mg per milligram of creatinine (mean ±SD) in the patients with HHRH, 0.34±0.07 in the subjects with idiopathic hypercalciuria, and 0.14±0.05 in normal subjects from the same tribe. Tubular reabsorption of phosphorus and serum phosphorus concentrations were 3.0 and 4.3 SD units below the age-related mean, respectively, in HHRH, and 1.1 SD units below the normal mean for both variables in idiopathic hypercalciuria. Mean serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D) were 303 pg per milliliter in HHRH and 145 pg per milliliter in idiopathic hypercalciuria (upper normal limit, 110). We conclude that the subjects with hypercalciuria and the patients with HHRH shared a hereditary renal phosphate leak that led to hypophosphatemia, elevated serum concentrations of 1,25-(OH)2D, increased intestinal calcium absorption, and hypercalciuria. The magnitude of the hypophosphatemia, which regulates 1,25-(OH)2D levels, appears to determine which subjects will have hypercalciuria alone and which will also have bone disease. (N Engl J Med 1987; 316:125–9.), A NEW syndrome, hereditary hypophosphatemic rickets with hypercalciuria (HHRH), was recently described in closely related members of a Bedouin tribe.1 It is characterized by rachitic skeletal deformities and abnormalities of phosphate and calcium metabolism. We have studied 50 additional asymptomatic, unselected members of the same tribe. Unexpectedly, about 40 percent of them were found to have “idiopathic” hypercalciuria, as well as a pattern of biochemical abnormalities similar to those of their relatives with HHRH. Quantitatively, however, the abnormalities were milder, and the relevant biochemical values were intermediate between those found in the members with HHRH and those in normal members…

Original languageEnglish
Pages (from-to)125-129
Number of pages5
JournalNew England Journal of Medicine
Volume316
Issue number3
DOIs
StatePublished - 15 Jan 1987

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