Public concern over
vitamin D deficiency has led to widespread use of over the counter (OTC)
vitamin D (-D3 or -D2) supplements, containing up to 10,000 IU/unit dose (400 IU=10μg). Overzealous use of such supplements can cause
hypercalcemia due to
vitamin D toxicity. Infants are particularly vulnerable to toxicity associated with
vitamin D overdose. OTC supplements are not subject to stringent quality control regulations from FDA and high degree of variability in
vitamin D content in OTC pills has been demonstrated. Other etiologies of
vitamin D induced
hypercalcemia include
hyperparathyroidism, granulomatous
malignancies like
sarcoidosis and mutations in the
CYP24A1 gene. The differential diagnosis of
hypercalcemia should include iatrogenic and genetic etiologies. C24-hydroxylation and C3-epimerization are two important biochemical pathways via which
25-hydroxyvitamin D3 (25(
OH)D3) is converted to its metabolites,
24,25-dihydroxyvitamin D3 (24,25(
OH)2D3) or its C3 epimer, 3-epi-25-OH-D3 respectively. Mutations in the
CYP24A1 gene cause reduced serum 24,25(
OH)2D3 to 25(
OH)D3 ratio (<0.02), elevated serum
1,25-dihydroxyvitamin D (
1,25(OH)2D3),
hypercalcemia,
hypercalciuria and
nephrolithiasis. Studies in infants have shown that 3-epi-25(OH)D3 can contribute 9-61.1% of the total 25(
OH)D3. Therefore, measurements of
parathyroid hormone (PTH) and
vitamin D metabolites 25(
OH)D3,
1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(
OH)2D3 are useful to investigate whether the underlying cause of
vitamin D toxicity is iatrogenic versus genetic. Here we report a case of
vitamin D3 associated toxicity in a 4-month-old female who was exclusively breast-fed and received an oral liquid
vitamin D3 supplement at a dose significantly higher than recommended on the label. The
vitamin D3 content of the supplement was threefold higher (6000 IU of D/drop) than listed on the label (2000 IU). Due to overdosing and higher
vitamin D3 content, the infant received ∼50,000 IU/day for two months resulting in severe
hypercalcemia,
hypercalciuria and
nephrocalcinosis. We also review the relevant literature on
vitamin D3 toxicity in this report.