Vitamin D-Dependent Rickets: Actions of Parathyroid Hormone and 25-Hydroxycholecalciferol

Abstract

ExtractDuring active rickets, the increase in 3',5'-adenosine monophosphate (3',5'-AMP) excretion after infusion of parathyroid hormone (PTH) can be claimed as a demonstration of PTH responsiveness, at least as far as the kidney is concerned (Table II). In patients with vitamin D-dependent rickets, following 25-HGC therapy, the basal excretion ratios of nanomoles 3',5'-AMP/milligrams creatinine fall within the normal range, and, although the basal ratios of milligrams phosphate/milligrams creatinine excretion decrease to normal (Tables III, IV, and V), a phosphaturic response to PTH is still not evident. The high basal ratios of nanomoles 3',5'-AMP/ milligrams creatinine and milligrams phosphate/milligrams creatinine suggest underlying hyperparathyroidism during a phase of this syndrome marked by hypocalcemia and hyperaminoaciduria. During 2-day PTH challenges, while rickets was active, the peak increases in serum calcium above base line were 1.92, 1.80, and 1.86 mg/100 ml. After treatment with 25-hydroxycholecalciferol (25-HCG), no further significant increases in serum calcium above base line could be elicited (Tables VI, VII, VIII). It would seem, therefore, that, while these patients were untreated, small but sufficient amounts of 25-HCC or another metabolite of vitamin D were available to permit the calcium-mobilizing action of PTH on bone. The observed hypocalcemia in vitamin D-dependent rickets, then, is most likely secondary to a defect in gastrointestinal absorption. Mineral balance studies during active rickets revealed an absorptive defect for calcium, phosphorus, and magnesium-a defect completely reversible after 25-HCC treatment. Speculation

Biological Activity of1-alpha-hydroxy Vitamin D<SUB>3</SUB>in Vitamin D Dependency

“…The validity of his hypothesis has been verified by other investigators (Stoop et al, 1967) (Tsuchiya et al, 1969) (Matsuda et al, 1969) (Hamilton et al, 1970) (Scriver, 1970) (Rosen et al, 1972) (Fraser et al, 1973) (Balsan et al, 1975 (Reade et al, 1975). Vitamin D dependent rickets and vitamin D dependency are its widely used synonyms.…”

Rickets and Alopecia with Resistance to 1,25-Dihydroxyvitamin D: Two Different Clinical Courses with Two Different Cellular Defects*

“…The two patients reported here have congenital alopecia with biochemical and radiologic features of vitamin D-dependent rickets (1)(2)(3)(4)(5)(6)(7). Their biochemical abnormalities included hypocalcemia, high circulating iPTH, hypophosphatemia, increased serum alkaline phosphatase, hyperaminoaciduria, and decreased renal tubular reabsorption of phosphate.…”

Response to Crystalline 1α-Hydroxyvitamin D3 in Vitamin D Dependency

“…It is the nature of recessive mendelian traits in man to exhibit genetic heterogeneity (9,28). Differcnccs in the maintenance requirement for 25-OH-D, and vitamin D, among patients with apparent vitamin D dependency have already been reported (35,38). A description of the cellular events which determine the vitamin D dependent trait might be obtained in more detail through investigation of a promising animal model in swine (19,30).…”