Vitamin D/dietary calcium deficiency rickets and pseudo-vitamin D deficiency rickets

Abstract

This review describes the pathogenesis, clinical presentation and biochemical perturbations found in privational (nutritional) rickets and pseudo-vitamin D deficiency rickets (PDDR), an autosomal recessive condition with loss of function mutations in CYP27B1. It may seem strange to combine a discussion on privational rickets and PDDR as a single topic, but privational rickets and PDDR present with similar clinical signs and symptoms and with similar perturbations in bone and mineral metabolism. Of interest is the characteristic lack of features of rickets at birth in infants with PDDR, a finding which has also been reported in infants born to vitamin D-deficient mothers. This highlights the independence of the fetus and neonate from the need for vitamin D to maintain calcium homeostasis during this period. The variable roles of vitamin D deficiency and dietary calcium deficiency in the pathogenesis of privational rickets are discussed and the associated alterations in vitamin D metabolism highlighted. Although PDDR is a rare autosomal recessive disorder, results of long-term follow-up are now available on the effect of treatment with calcitriol, and these are discussed. Areas of uncertainty, such as should affected mothers breastfeed their infants, are emphasized.

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

“…In both conditions the child is fated to develop hypocalcemia, hypophosphatemia, and rickets. VDDR-I presents within the first 3-12 mo after birth; VDDR-II can also present in infancy but has often been diagnosed during the second year or even later (36,66,230,258,312,538,621,662,665,727). Mortality can also occur in infancy or childhood due to the severity of the hypocalcemia (36,374).…”

“…Mortality can also occur in infancy or childhood due to the severity of the hypocalcemia (36,374). Pseudofractures and fractures can occur in both conditions, but bowing of the long bones and metaphyseal widening are much more common (36,66,180,230,258,312,408,538,621,662,665,727).…”

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

“…Severe vitamin D deficiency in children, due to lack of exposure of sunlight and low vitamin D intake, is still endemic in several areas of the world (166,369). In these children, serum 25OHD levels are usually below 10 ng/ml, which is considered as the threshold for 25OHD to control intestinal calcium absorption (55,325).…”

1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components

“…As the elaboration of these hormones is modulated directly by the calcium content in the blood, the activities of 1,25(OH) 2 D 3 in the intestine, kidney, and bone as well as other target tissues are linked directly to the levels of calcium and phosphate that are present in the extracellular compartment. Interestingly, although the vast majority of these fundamental principles of calcium homeostasis has been defined through studies in animal models as well as in humans over several decades (5,6), the phenotypes of a number of genetically modified murine models are currently providing important new insights. These models include strains which contain crippling genomic mutations in either the Cyp27b1 (7,8) or the Vdr genes (9 -12) that closely replicate the molecular defects observed and characterized in humans.…”