Response to crystalline 1alpha-hydroxyvitamin D3 in vitamin D dependency.
The therapeutic response to chemically synthesized 1alpha-hydroxycholecalciferol (1alpha-OH-D3) was studied in three patients with autosomal recessive vitamin D dependency (ARVDD).  The daily maintenance dose for vitamin D2, to prevent signs of vitamin D deficiency in these patients, was 40-54.4 mug/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D2 resulted in the ultimate reappearance of the vitamin D depletion syndrome in patients 1 and 2 (Figs. 1 and 2).  The third patient presented with the deficiency syndrome despite adequate vitamin D nutrition and was recognized to have ARVDD.  Treatment with 1alpha-OH-D3 by mouth in all three patients at dose levels of 1-3 mug/24 hr (80-100 ng/kg) corrected hypocalcemia and suppressed parathyroid hormone-dependent renal loss of amino acids (Figs. 1, 2, and 4).  Rickets healed in 7-9 weeks on 1alpha-OH-D3 alone (Fig. 3).  The therapeutic response was rapid.  It was usually seen first in the rise of serum calcium (Figs. 5 and 6).  Withdrawal of 1alpha-OH-D3 was followed first by a fall of serum phosphorus, then by a fall in serum calcium; the latter occurred within about 2 weeks of withdrawal.  Because the synthesis of 1alpha-OH-D3 is simpler than for 1alpha,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal 1alpha-OH-D3 to be the agent of choice for treatment of this and analogous diseases.
D000469:Alkaline Phosphatase / Q000032:analysis; D002118:Calcium / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003460:Crystallization; D004097:Dihydrotachysterol / Q000627:therapeutic use; D005260:Female; D006128:Growth; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage* / Q000627:therapeutic use; D006961:Hyperparathyroidism / Q000188:drug therapy; D007223:Infant; D010758:Phosphorus / Q000097:blood; D011859:Radiography; D000608:Renal Aminoacidurias / Q000188:drug therapy; D014808:Vitamin D Deficiency / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism
D006887:Hydroxycholecalciferols; D010758:Phosphorus; D000469:Alkaline Phosphatase; D004097:Dihydrotachysterol; D002118:Calcium