Table 1 Main differential diagnoses of FGF23-mediated hypophosphataemia

From: Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia

Disease (gene)	Clinical signs and symptoms	Biochemical parameters							Radiographic characteristics
Disease (gene)	Clinical signs and symptoms	FGF23^a	1,25(OH)₂D	Ca²⁺	PTH	ALP	Calciuria^b	Comment	Radiographic characteristics
*Genetic forms*
XLH (PHEX)	Rickets, dental abscesses, enthesopathy, articular pain	↑ or normal	Normal^c	Normal	Normal or ↑	↑	↓	NA	Dense bones, ↑BMD, pseudofractures, enthesopathy, early osteoarthritis
ADHR (FGF23)	Variable expression	↑ or normal^d	Normal^c	Normal	Normal or ↑	↑	↓	NA	NA
ARHR type 1 (DMP1)	Can be present as sclerosing bone disease	↑ or normal	Normal^c	Normal	Normal or ↑	↑	↓	NA	Dense vertebral bodies
ARHR type 2 (ENPP1)	Generalized arterial calcifications, with or without multisystem manifestations	↑ or normal	Normal^c	Normal	Normal or ↑	↑	↓	NA	Generalized arterial calcifications
ARHR type 3 (FAM20C)	Cerebral calcifications, perilacunar osteomalacia on bone biopsy, peculiar facial features	↑ or normal	Normal^c	Normal	Normal or ↑	↑	Unknown	NA	Dense bones, ↑BMD, pseudofractures, enthesopathy
α-Klotho translocation (KL translocation)	Macrocephaly, prominent forehead, dysplasia of the nasal bones with exaggerated midfacial protrusion	↑	Normal^c	Normal	↑	↑	↓	α-Klotho translocation is associated with more severe hypophosphataemia than XLH	Rickets
Fibrous dysplasia – McCune–Albright syndrome (somatic GNAS)	Café-au-lait spots or naevi, focal bone lesions	Normal or ↑	Normal^c	Normal or ↓	Normal or ↑	↑	↓	Hyperfunctioning endocrinopathies	Focal bone lesions
Cutaneous skeletal hypophosphataemia syndrome (somatic RAS genes)	Mosaic skeletal dysplasia, epidermal naevi and moles	Normal or ↑	Normal^c	Normal or ↓	Normal or ↑	↑	↓	Possible development of tumours	NA
Osteoglophonic dysplasia (FGFR1) or opsismodysplasia (INPPL1)	Very short stature, severe skeletal dysplasia	Normal	Normal^c	Normal	Normal or ↑	↑ or normal	Normal	NA	Severe bone dysplasias, non-ossifying bone lesions, hypodontia
SGK3 mutation	Rickets	NA	NA	NA	NA	NA	NA	Unclear pattern	Rickets
*Acquired forms*
Intravenous iron preparation use	In the context of iron deficiency with parenteral administration of iron	NA	NA	NA	NA	NA	NA	↑Intact FGF23; ↓C-terminal FGF23	Rickets and/or osteomalacia are uncommon
TIO	No family history of rickets or osteomalacia, no dental manifestations	Normal or ↑	Normal^c	Normal or ↓	Normal or ↑	↑	↓	NA	Rickets and/or osteomalacia

↑, elevated; ↓, decreased; 1,25(OH)2D, 1,25-dihydroxyvitamin D; ADHR, autosomal dominant hypophosphataemic rickets; ALP, alkaline phosphatase; ARHR, autosomal recessive hypophosphataemic rickets; BMD, bone mineral density; FGF23, fibroblast growth factor 23; NA, not available; PTH, parathyroid hormone; TIO, tumour-induced osteomalacia; XLH, X-linked hypophosphataemia. ^aIntact FGF23. ^b24-h urinary calcium excretion. ^cDecreased relative to the serum concentration of phosphate. ^dFGF23 varies with iron deficiency.

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Table 1 Main differential diagnoses of FGF23-mediated hypophosphataemia

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