Clinical Manifestations of Vitamin D Deficiency

Vitamin D is an essential nutrient that plays an important role in calcium homeostasis and bone health. Severe deficiency of vitamin D causes rickets and/or hypocalcemia in infants and children and osteomalacia in adults or adolescents after epiphysial closure; severe vitamin D deficiency may also be associated with hypocalcemia, which may cause tetany or seizures. These disorders occur with the highest frequency among children in malnourished populations and in children with chronic illnesses. Rickets also occurs in children in developed nations if sufficient vitamin D intake is not ensured through the use of supplements and fortified foods, particularly if exposure to sunlight is limited. Vitamin D deficiency causes rickets in growing children, and osteomalacia in adolescents and adults. 

Rickets refers to a failure of mineralization of growing bone and cartilage and, depending on the severity, the child may be asymptomatic, or present with varying degrees of pain and irritability, motor delays, poor growth, and increased susceptibility to infections. Younger children may manifest with delayed closure of fontanelles, craniotabes, frontal bossing, prominence of costochondral junctions, widening of wrists and ankles, and bow legs or knock knees (genu valgum or varum). 

Radiological features of rickets include low bone density, loss of the demarcation between the metaphyses and growth plate and loss of the provisional zone of calcification, widening of the growth plate (from proliferation of uncalcified cartilage and osteoid), and metaphyseal widening, splaying, cupping, and fraying.

In older adolescents and adults, growth is complete, epiphyseal plates are fused, and there is usually reserve mineral, all of which help prevent bony deformities. Impaired mineralization in older children and adults causes osteomalacia, which may be asymptomatic or manifest as isolated or generalized muscle and bone pain.

Biochemical changes 
Vitamin D deficiency reduces intestinal calcium and phosphorus absorption. Parathyroid hormone (PTH) increases, leading to mobilization of calcium from bone so that serum calcium levels remain normal or are moderately decreased.

With more severe vitamin D deficiency, calcium and phosphorus levels are normal or moderately decreased, 25(OH)D levels decrease, and PTH and ALP levels increase. 1,25(OH)2D levels initially increase in response to rising levels of PTH, but may subsequently decrease because its substrate 25(OH)D is limited.

Low serum phosphorus levels may cause muscle weakness and discomfort, and children may have difficulty standing or walking. Low phosphorus also prevents apoptosis of hypertrophic chondrocytes, causing disorganization of the growth plate. The reduced serum levels of calcium and phosphorus lead to a lower calcium-phosphorus product and the subsequent mineralization defects in growing children that are characteristic of rickets. 

Patients with advanced vitamin D-deficient rickets may develop severe hypocalcemia especially during periods of very rapid growth, such as infancy and adolescence, when increased calcium mobilization from bone from rising levels of PTH and 1,25(OH)2D is unable to keep pace with increased calcium needs. This can lead to seizures or tetany, or may present as apneic spells, stridor, wheezing, hypotonia, and hyperreflexia, particularly in very young children.

Reference: UTD

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