Non-nutritional rickets: Approach, precision medicine, and outcomes

Figure 3 Algorithm for etiological diagnosis of rickets using biochemical tests. ¹Exception: Raised alkaline phosphatase in mucolipidosis. ²In the clinical context of established nutritional deficiency or risk factors for vitamin D deficiency. ³Differentiation between fibroblast growth factor 23 (FGF-23) mediated hypophosphatemic ricket and non FGF-23 mediated hypophosphatemic ricket may be made using FGF-23 assays or urinary Ca creatinine ratio or 1,25-dihydroxyvitamin D. ⁴Requires polymerase chain reaction for diagnosis. ⁵Rule out hypothyroidism and growth hormone deficiency. Ca: Calcium; PO₄: Phosphorus; ALP: Alkaline phosphatase; 25(OH)D: 25-hydroxyvitamin D; PTH: Parathyroid hormone; CR: Calciopenic ricket; NR: Nutritional ricket; VDDR1B: Vitamin D dependent rickets type 1B; VDDR3: Vitamin D dependent rickets type 3; FGF-23: Fibroblast growth factor 23; HR: Hypophosphatemic rickets; JMC: Jansen metaphyseal chondrodysplasia; KL: Klotho; ARHR2: Autosomal recessive hypophosphatemic rickets 2; 1,25(OH)₂D: 1,25-dihydroxyvitamin D; HP: Hypophosphatasia; PHP: Pseudo hypophosphatasia; RM: Rickets mimicker; CKD: Chronic kidney disease; dRTA: Distal renal tubular acidosis; pRTA: Proximal renal tubular acidosis; FS: Fanconi syndrome; LMW: Low-molecular-weight; NGS: Next-generation sequencing; VDDR1A: Vitamin D dependent rickets type 1A; VDDR3: Vitamin D dependent rickets type 3; VDDR2A: Vitamin D dependent rickets type 2A; VDDR2B: Vitamin D dependent rickets type 2B; TMD: Tibia metaphyseal-diaphyseal; MPS: Mucopolysaccharidosis; GAG: Glycosaminoglycans; ED: Epiphyseal dysplasia; SED: Spondyloepiphyseal dysplasia; SMD: Spondylometaphyseal dysplasia; CAKUT: Congenital anomalies of the kidney and urinary tract; DM: Diabetes mellitus; SNHL: Sensorineural hearing loss; DIP: Distal interphalangeal joint; PIP: Proximal interphalangeal joint; SGA: Small for gestational age.