Table 5.

Characteristics and laboratory findings of inherited and acquired causes of phosphopenic rickets, modified from Ref:[330,331] Abbreviations are as follows: 1α,25(OH)2D, 1,25-dihydroxyvitamin D; 25(OH)D, cholecalciferol; 24,25(OH)2D3, 24,25-dihydroxyvitamin D3; ALP, alkaline phosphatase; Ca, serum levels of calcium; FGF23, fibroblast growth factor 23; N, not applicable; PO4, serum levels of phosphate; PTH, parathyroid hormone; TmP/GFR, maximum rate of renal tubular reabsorption of phosphate per glomerular filtration rate; U-Ca, urinary calcium excretion; U-PO4, urinary phosphate excretion; VDR, vitamin D receptor.

Disorder	Gene	Ca	PO4	ALP	U-Ca	U- PO4	TmP/ GFR	FGF23	PTH	25 (OH) D	1α,25 (OH)2D	pathogenesis
FGF23-mediated hypophosphatemia (phosphopenic rickets and /or osteomalacia due to elevated FGF23 and / or signaling)
X-linked hypophosphatemia (XLH)	PHEX (Xp22.1)	N	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in bone
Autosomal dominant hypophosphatemic rickets (ADHR)	FGF23 (12p.13.3)	N	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	FGF23 protein resistant to degradation
Autosomal recessive hypophosphatemic rickets 1 (ARHR1)	DMP1 (4q22.1)	N	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in bone
Autosomal recessive hypophosphatemic rickets 2 (ARHR2)	ENPP1 (6q23.2)	N	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in bone
McCune-albright syndrome /fibrous dysplasia	GNAS (20q13.3)	N,↓	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in bone
Raine syndrome related hypophosphatemia (ARHR3)	FAM20C (7q22.3)	N	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in bone
Tumor induced osteomalacia (TIO)	NA	N,↓	↓	↑,↑↑	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in tutor cells
Osteoglophonic dysplasia (OGD)	FGFR1 (8p11.23)	N	↓	↑,N	↓	↑	↓	N,↑	N,↑	N	↓,N(*)	↑ FGF23 expression in bone
Cutaneous skeletal hypophosphatemia syndrome (SFM)	RAS (1p13.2)		↓	↑,↑↑	↓	↑	↓	N	N,↑	N	N	Unknown
	KLOTHO (13q13.1)		↓	↑,↑↑	↓	↑	↓	↑	↑↑	N	N
Non FGF23-mediated hypophosphatemia (phosphopenic rickets and /or osteomalacia due to primary tubular phosphate wasting)
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)	SLC34A3	N	↓	↑,↑↑	↓	N,↑	↑	↓	↓	N,↓	↑↑	Loss of function of NaPi2c in the proximal tubule
x-linked recessive hypophosphatemic rickets	CLCN5	N	↓	↑,↑↑	N,↑	↑	↓	Varies	Varies	N	↑	Loss of function of CLCN5 in the proximal tubule
Hypophosphatemia and nephrocalciniosis and Fanconi reno-tubula syndrome 2	SLC34A1	N	↓	↑,↑↑	↑	↑	↓	↓	Varies	N	↑	Loss of function of NaPi2c in the proximal tubule
Hereditary forms of Fanconi syndrome	CTNS	N,↓	↓	↑,↑↑	N,↑	↑	N,↑	N,↑	N,↑	N	N	Cysteine accumulation in the proximal tubule
Iatrogenic proximal tubulopathy	–	N	↓	↑,↑↑	Varies	↑	↓	↓	Varies	N	↑	Drug toxicity

^(*)Inappropriately normal relative to decreased serum phosphate concentration