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Plasma levels of 25-hydroxyvitamin D (25-OHD) have been measured in mothers and their premature infants with neonatal hypocalcemia. In 11 of 15 mother-premature pairs, plasma levels of 25-OHD were remarkably low in both mother and infant. The present data suggest a nutritional basis for the abnormal biochemical findings in these mothers. Secondary vitamin D deficiency in premature infants of these mothers appears to play a significant, but not exclusive, role in the pathogenesis of this syndrome. During pregnancy, nutritional vitamin D deficiency may be more common in this population than is currently realized.

During 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-HCC 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.

Extract: During 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-HCC 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: We suggest that the small intestine represents the prime target organ site for impaired vitamin D action in this disease by differential failure in the biologic formation of 1,25-dihydroxycholecalciferol from 25-HCC. Similarly, we postulate that a variable hydroxylating deficiency may be present in the transformation of vitamin D3to 25-HCC. Genetic heterogeneity, therefore, may ultimately explain common responses in these three patients to contrasting doses of dihydrotachysterol (DHT) and 25-HCC.