Vitamin D Deficiency and Toxicity – Top USMLE Diseases

X-linked hypophosphatemic rickets (XLHR) is the most common of several hereditary disorders and is characterized by renal phosphate wasting, resulting in weak or soft bones. Formerly known as “vitamin D-resistant rickets,” XLHR is not currently considered true vitamin D resistance (related to inherited defects in the vitamin D metabolic pathway or calcitriol receptor). Typical clinical presentations occur during childhood and manifest as short stature, genu valgum, bone pain, and dental pain. Diagnosis is made by lab studies and confirmed by identification of the mutation in the PHEX gene. Management includes high doses of activated vitamin D (calcitriol) and phosphate. Patient monitoring by a multidisciplinary team is crucial to ensure adequate growth.

Fat-soluble vitamins are absorbed and stored in adipose tissue (fat) and the liver. These vitamins can be released from storage and used when necessary. The 4 important fat-soluble vitamins are A, D, E, and K. Each vitamin has its own function, and deficiencies can lead to significant clinical manifestations. Diagnosis of deficiencies is by clinical presentation and lab testing, and management of vitamin deficiency is with supplementation. Because these vitamins are fat-soluble and stored in the body, overuse of supplemental vitamins may lead to toxicity and adverse effects, especially with vitamins A and D.

Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children, while osteomalacia affects the sites of bone turnover in children and adults. Although most cases of rickets and osteomalacia are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities, while osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Diagnosis is made based on a combination of clinical findings, laboratory tests and imaging. Treatment includes vitamin D, calcium, and phosphorus supplementation.