Cutoff value of serum 25-hydroxyvitamin D leading to vitamin D deficiency for children in Japan.

The 25-hydroxyvitamin D [25(OH)D] level and clinical symptoms are used to diagnose vitamin D deficiency (VDD). The current 25(OH)D cutoff value is based on biochemical findings, such as elevated parathyroid hormone (PTH) levels, rather than clinical symptoms. However, low 25(OH)D levels do not necessarily produce clinical symptoms. The present study proposed a 25(OH)D cutoff value for diagnosing manifest VDD, defined as VDD that is diagnosable based on either clinical symptoms, such as rickets and/or hypocalcemia (symptomatic VDD), or biochemical findings, such as elevated PTH and alkaline phosphatase levels (biochemical VDD). One hundred and eighty participants aged 0-15 yr with suspected VDD were enrolled, and receiver operating characteristic curve analysis was performed. Sixty-seven and ten patients had symptomatic and biochemical VDD, respectively. A chemiluminescent immunoassay, which demonstrated good correlation with liquid chromatography-tandem mass spectrometry, determined the 25(OH)D cutoff value for manifest VDD to be 37.5 nmol/L (15.0 ng/mL), with a sensitivity and specificity of 81% and 97%, respectively. Twenty percent (19/94) of participants with 25(OH)D ≤ 37.5 nmol/L were asymptomatic. In cases with 25(OH)D ≤ 37.5 nmol/L, a low urinary calcium-to-creatinine ratio was a risk factor for manifest VDD. In conclusion, the 25(OH)D cutoff value leading to manifest VDD for children in Japan was 37.5 nmol/L.