Differential diagnosis of vitamin D ‐related hypercalcemia using serum vitamin D metabolite profiling
AbstractGenetic causes of vitamin D ‐related hypercalcemia are known to involve mutation of 25‐hydroxyvitamin D‐24‐hydroxylaseCYP24A1 or the sodium phosphate co ‐transporterSLC34A1; which result in excessive 1,25 ‐(OH)2D hormonal action. However, at least 20% of idiopathic hypercalcemia (IH) cases remain unresolved. In this case ‐control study, we used precision vitamin D metabolite profiling based on LC‐MS/MS of an expanded range of vitamin D metabolites ‐ to screen German and French cohorts of hypercalcemia patients, to identify patients with altered vitamin D metabolism where involvement ofCYP24A1 orSLC34A1 mutation had been ruled out, and possessed normal 25 ‐OH‐D3:24,25 ‐(OH)2D3 ratios. Profiles were compared to those of hypercalcemia patients with hypervitaminosis D, Williams ‐Beuren syndrome (WBS),CYP24A1 mutation, and normal subjects with a range of 25 ‐OH‐D levels. We observed that certain IH and WBS patients exhibited a unique profile comprising 8‐10‐fold higher serum 23,25,26‐(OH)3D3 and 25 ‐OH‐D3‐26,23‐lactone than normals; as well as very low serum 1,25‐(OH)2D3 (2 ‐5 pg/mL) and elevated 1,24,25‐(OH)3D3, which we interpret implies hypersensitive expression of vitamin D ‐dependent genes, including CYP24A1, as a general underlying mechanism of hypercalcemia in these patients. As serum 25‐OH‐D3 and 24,25 ‐(OH)2D3 remained normal, we excluded the possibility that the aberrant profile was caused by hypervitamino...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Martin Kaufmann,
Karl ‐Peter Schlingmann,
Linor Berezin,
Arnaud Molin,
Jesse Sheftel,
Melanie Vig,
John C. Gallagher,
Akiko Nagata,
Shadi Sedghi Masoud,
Ryota Sakamoto,
Kazuo Nagasawa,
Motonari Uesugi,
Marie Laure Kottler,
Martin Konrad,
G Tags: Original Article Source Type: research
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