Patients with
vitamin D-dependent rickets type 1A (
VDDR1A) are usually treated with
alfacalcidol, an analog of
vitamin D. Around puberty, an increased dose of
alfacalcidol is recommended for these patients to avoid
hypocalcemia and
secondary hyperparathyroidism. However, no indicators of
secondary hyperparathyroidism except for PTH are presently known. The aim of this study is to evaluate whether urinary
calcium to
creatinine ratio (U-Ca/Cr) is useful as a
biomarker of
secondary hyperparathyroidism in
VDDR1A patients in order to determine the proper dose of
alfacalcidol. Two brothers with
VDDR1A were recruited who had null mutations of
CYP27B1 which encodes 1-alpha-hydroxylase of
vitamin D. We investigated the relationship between U-Ca/Cr and intact-PTH around puberty when the brothers showed
hypocalcemia with
secondary hyperparathyroidism. The results were compared to those of five patients with
vitamin D deficiency (VDD). As a result, high intact-PTH levels were observed when U-Ca/Cr decreased to less than 0.1 (mg/mg) in both
VDDR1A brothers. This relationship was also observed in the VDD patients. However, it is necessary to take into account body
calcium status, either in depletion or in excess, to accurately evaluate the relationship between U-Ca/Cr and
secondary hyperparathyroidism. First, low U-Ca/Cr was detected in situations with
calcium depletion without
hyperparathyroidism in the
VDDR1A patients. Second, high U-Ca/Cr with
hyperparathyroidism could be detected theoretically in a condition of excess
calcium supply. In conclusion, a U-Ca/Cr ratio of less than 0.1 (mg/mg) in
VDDR1A patients is useful to accurately evaluate
calcium depletion and
secondary hyperparathyroidism.