ExtractThe therapeutic response to chemically synthesized 1α-hydroxy-cholecalciferol (1α-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 40–54.5 μ/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D2resulted in the ultimate reappearance of the vitamin D depletion syndrome inpatients 1and2(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 1α-OH-D3by mouth in all three patients at dose levels of 1–3 μg/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 1α-OH-D3alone (Fig. 3) The therapeutic response was rapid. It was usually seen first in the rise of serum calcium (Figs. 5 and 6). Withdrawal of 1α-OH-D3was 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 1α-OH-D3is simpler than for 1α,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal 1α-OH-D3to be the agent of choice for treatment of this and analogous diseases.SpeculationVitamin D dependency or pseudodeficiency rickets is believed to be an inborn error of vitamin D hormone biosynthesis. The putative abnormal enzyme is 25-hydroxycholecalciferol 1-hydroxylase in the recessively inherited trait. Consequently, this experiment of nature offers a special opportunity to examine the requirement in human subjects, for 1α -hydroxyvitamin D3, metabolites.