Table 1. Characteristic features of various forms of hypophosphatemic rickets.

	XLHR	ADHR	ARHR1 ARHR2	HHRH	NPHLOP1 NPHLOP2	HRH
Gene involved	PHEX	FGF23	DMP1 and ENPP1, respectively	SLC34A3	SLC34A1 and SLC9A3R1, respectively	KL
Chromosomal location	Xp22.1	12p13	4q22.1 and 6q23.2	9q34.3	5q35.3 and 17q25.1	13q13.1
Inheritance	X-linked dominant	Autosomal dominant	Autosomal recessive	Autosomal recessive	Autosomal dominant	Autosomal dominant
Type of mutation	Loss of function	Gain of function	Loss of function	Loss of function	Loss of function	Chromosomal translocation t (9;13)(q21.13;q13.1)
Pathogenesis	PHEX mutations raise FGF23 levels causing renal phosphate wasting	Mutated FGF23 becomes resistant to proteolytic inactivation, increasing FGF23 levels, causing renal phosphate wasting	DMP1 and ENPP1 mutations increase FGF23 levels causing renal phosphate wasting	SLC34A3 mutations decrease renal phosphate reabsorption causing renal phosphate wasting	Inactivating SLC34A1 and SLC9A3R1 mutations decrease renal phosphate reabsorption causing renal phosphate wasting	Chromosomal translocation breakpoint adjacent to α-Klotho results in elevated circulatory α-Klotho and FGF23 levels causing renal phosphate wasting and hyperparathyroidism
Serum phosphorus	Low	Low	Low	Low	Low	Low
Urine phosphorus	High	High	High	High	High	High
Serum calcium	Normal	Normal	Normal	Normal/High	Normal	Normal/High
Urine calcium	Low/Normal	Low/Normal	Low/Normal	High	High	Normal/High
Serum FGF23 level	High	High	High	Normal	Normal	High
1,25 (OH) 2 vitamin D 3 level	Low/Normal	Low/Normal	Low/Normal	High	High	Low/Normal
Parathyroid hormone	Normal/High	Normal	Normal	Low	Low/Normal	High
TmP/GFR a	Low	Low	Low	Low	Low	Low
Muscle weakness	Minimal	Present	Minimal	Present	Present	Present
Hypercalciuria	No	No	No	Yes	Yes	Yes
Nephrolithiasis	No	No	No	Yes	Yes	Yes
Nephrocalcinosis	No	No	No	Yes	Yes	Yes

Abbreviations: ADHR, autosomal dominant hypophosphatemic rickets; ARHR, autosomal recessive hypophosphatemic rickets; FGF, fibroblast growth factor; GFR, glomerular filtration rate; HRH, hypophosphatemic rickets with hyperparathyroidism; HHRH, hereditary hypophosphatemic rickets with hypercalciuria; NPHLOP, hypophosphatemic nephrolithiasis/osteoporosis type; TmP, tubular maximum reabsorption of phosphate; XLHR, X-linked hypophosphatemic rickets.

^a TmP/GFR is the ratio of tubular maximum reabsorption of phosphate (TmP) to the glomerular filtration rate (GFR). ^{40 41} It is used to evaluate renal phosphate transport, and low values suggest renal phosphate wasting. ⁴²