Available online 30 January 2024, 101876

Vitamin D is mainly produced in the skin (cholecalciferol) as result of sun exposure while a fraction of it is obtained from dietary sources (ergocalciferol). Vitamin D is further processed to 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D (calcitriol) in the liver and kidneys, respectively. Calcitriol is the active form which mediates the actions of vitamin D via vitamin D receptor (VDR) which is present ubiquitously. Defect at any level in this pathway leads to vitamin D deficient or resistant rickets. Nutritional vitamin D deficiency is the leading cause of rickets and osteomalacia worldwide and responds well to vitamin D supplementation. Inherited disorders of vitamin D metabolism (vitamin D-dependent rickets, VDDR) account for a small proportion of calcipenic rickets/osteomalacia. Defective 1α hydroxylation of vitamin D, 25 hydroxylation of vitamin D, and function of vitamin D receptor result in VDDR1A, VDDR1B and VDDR2A, respectively whereas defective binding of vitamin D to vitamin D response element due to overexpression of heterogeneous nuclear ribonucleoprotein and accelerated vitamin D metabolism cause VDDR2B and VDDR3, respectively. Impaired dietary calcium absorption and consequent calcium deficiency increases parathyroid hormone in these disorders resulting in phosphaturia and hypophosphatemia. Hypophosphatemia is a common feature of all these disorders, though not a sine-qua-non and leads to hypomineralisation of the bone and myopathy. Improvement in hypophosphatemia is one of the earliest markers of response to vitamin D supplementation in nutritional rickets/osteomalacia and the lack of such a response should prompt evaluation for inherited forms of rickets/osteomalacia.

Vitamin D, is mainly produced in the skin as a result of sun exposure. On exposure to ultraviolet B (~290-315 nm) sun-rays, 7-dehydrocholesterol (pro-vitamin D3) in the skin is converted to pre-vitamin D3 and then thermally isomerizes to vitamin D3 to enter the circulation. Vitamin D3 binds with vitamin D binding protein in circulation and is transported to the liver where it is converted into 25-hydroxyvitamin D (25OHD). Hydroxylation at position 25 of vitamin D is mainly carried out by

To summarise, hypophosphatemia is a common feature of vitamin D deficiency, resistance and related disorders. Hypophosphatemia plays an important role in the defective mineralization in all these calcipenic disorders. However, serum phosphorus is often normal or even rarely, elevated leading to misdiagnosis as pseudohypoparathyroidism. Adequate therapy and reduction of PTH corrects hypophosphatemia in all calcipenic disorders. Correction of hypophosphatemia is one of the earliest and reliable

Saba Samad Memon, Manjunath Doddamani

© 2024 Published by Elsevier Ltd.