scholarly journals Overlapping Phenotypes Associated With CYP24A1, SLC34A1, and SLC34A3 Mutations: A Cohort Study of Patients With Hypersensitivity to Vitamin D

2021 ◽  
Vol 12 ◽  
Author(s):  
Arnaud Molin ◽  
Sandrine Lemoine ◽  
Martin Kaufmann ◽  
Pierre Breton ◽  
Marie Nowoczyn ◽  
...  
Keyword(s):  
Vitamin D ◽  
Medical History ◽  
Mineral Metabolism ◽  
Specific Pattern ◽  
Normal Serum ◽  
Heterozygous Mutation ◽  
Uncertain Significance ◽  
Normal Serum Calcium ◽  
Biallelic Mutations

Mutations in CYP24A1 (vitamin D 24-hydroxylase) and SLC34A1 (renal phosphate transporter NPT2a) cause autosomal recessive Infantile Hypercalcemia type 1 and 2, illustrating links between vitamin D and phosphate metabolism. Patients may present with hypercalciuria and alternate between chronic phases with normal serum calcium but inappropriately high 1,25-(OH)2D and appropriately low PTH, and acute phases with hypercalcemia with suppressed PTH. Mutations in SLC34A3 and SLC9A3R1 have been associated with phosphate wasting without hypercalcemia. The aims of this study were to evaluate the frequency of mutations in these genes in patients with a medical history suggestive of CYP24A1 mutation to search for a specific pattern. Using next generation sequencing, we screened for mutations in 185 patients with PTH levels < 20 pg/mL, hypercalcemia and/or hypercalciuria, and relatives. Twenty-eight (15%) patients harbored biallelic mutations in CYP24A1 (25) and SLC34A3 (3), mostly associated with renal disease (lithiasis, nephrocalcinosis) (86%). Hypophosphatemia was found in 7 patients with biallelic mutations in CYP24A1 and a normal phosphatemia was reported in 2 patients with biallelic mutations in SLC34A3. Rare variations in SLC34A1 and SLC34A3 were mostly of uncertain significance. Fifteen patients (8%) carried only one heterozygous mutation. Heterozygous relatives carrying SLC34A1 or SLC34A3 variation may present with biochemical changes in mineral metabolism. Two patients’ genotype may suggest digenism (heterozygous variations in different genes). No variation was found in SLC9A3R1. As no specific pattern can be found, patients with medical history suggestive of CYP24A1 mutation should benefit from SLC34A1 and SLC34A3 analysis.

scholarly journals Chronic Kidney Disease –Mineral Bone Disorder (CKD- MBD) – Further Insight at the Indian patients.

JMS SKIMS ◽  
2019 ◽  
Vol 22 (3) ◽  
Author(s):  
Muzaffar Maqsood Wani ◽  
Imtiyaz Ahmad Wani
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Mineral Metabolism ◽  
Left Ventricular ◽  
Normal Serum ◽  
Vitamin D Metabolism ◽  
Mineral Bone Disorder ◽  
Bone Disorder ◽  
Normal Serum Calcium

The kidneys play an important role in maintaining normal serum calcium (Ca) and phosphorous (P) concentrations. Chronic kidney disease (CKD) is associated with significant disturbances in bone and mineral metabolism, leading to altered serum concentrations of Ca, P, vitamin D and parathyroid hormone (PTH)1,2,3. These changes are initially detected when the glomerular filtration rate (GFR) falls to ≤60 mL/min and are nearly uniform as GFR drops to <30ml/min2,3. This leads to a number of bone abnormalities previously called “renal osteodystrophy”, renamed as CKD-Mineral Bone Disorder (CKD-MBD) by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) consensus group4 . CKD-MBD is a systemic disorder manifested by either one or a combination of a) abnormalities of Ca, P, PTH or vitamin D metabolism, b) abnormalities in bone turnover, mineralization, volume, linear growth or strength c) vascular or soft tissue calcification. This has over time been expanded to include left ventricular hypertrophy, hypertension, immune dysfunction and inflammation5,6. 

IDIOPATHIC HYPERCALCEMIA

PEDIATRICS ◽  
1959 ◽  
Vol 24 (2) ◽  
pp. 258-269
Author(s):  
David W. Smith ◽  
Robert M. Blizzard ◽  
Harold E. Harrison
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Normal Serum ◽  
Early Infancy ◽  
Serum Assay ◽  
Supplemental Vitamin ◽  
Normal Serum Calcium

A case of idiopathic hypercalcemia present from early infancy and diagnosed at 5 years of age is reported in which the serum assay of vitamin D indicated elevated levels. After discontinuation of supplemental vitamin D and a diet low in calcium the concentrations of calcium and vitamin D in the serum gradually returned to normal over a period of 18 months. Roentgenograms of the bones showed evidence of demineralization rather than increased density as reported in other cases of "idiopathic" hypercalcemia. During a subsequent 2-year follow-up the patient has maintained a normal serum calcium. The etiology is discussed with particular reference to the role of vitamin D in this case

scholarly journals Vitamin D deficiency in rats with normal serum calcium concentrations.

1982 ◽  
Vol 79 (15) ◽  
pp. 4791-4794 ◽  
Author(s):  
G. E. Lester ◽  
C. J. VanderWiel ◽  
T. K. Gray ◽  
R. V. Talmage
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Serum Calcium ◽  
Normal Serum ◽  
Normal Serum Calcium

scholarly journals FGF-23/Vitamin D Axis in Type 1 Diabetes: The Potential Role of Mineral Metabolism in Arterial Stiffness

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140222 ◽  
Author(s):  
Gemma Llauradó ◽  
Ana Megia ◽  
Albert Cano ◽  
Olga Giménez-Palop ◽  
Inmaculada Simón ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Arterial Stiffness ◽  
Potential Role ◽  
Mineral Metabolism ◽  
Fgf 23

Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology

2009 ◽  
Vol 297 (5) ◽  
pp. F1192-F1198 ◽  
Author(s):  
Tomer Meir ◽  
Ronen Levi ◽  
Liesbet Lieben ◽  
Steven Libutti ◽  
Geert Carmeliet ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Vitamin D Receptor ◽  
Normal Serum ◽  
Calcium Receptor ◽  
Collagen Crosslinks ◽  
Limited Role ◽  
Normal Serum Calcium ◽  
Total Body ◽  
Serum Pth

1,25(OH)2D3 decreases parathyroid hormone (PTH) gene transcription through the vitamin D receptor (VDR). Total body VDR−/− mice have high PTH levels, hypocalcemia, hypophosphatemia, and bone malformations. To investigate PTH regulation by the VDR specifically in the parathyroid, we generated parathyroid-specific VDR knockout mice ( PT-VDR−/−). In both strains, there was a decrease in parathyroid calcium receptor (CaR) levels. The number of proliferating parathyroid cells was increased in the VDR−/− mice but not in the PT-VDR−/− mice. Serum PTH levels were moderately but significantly increased in the PT-VDR−/− mice with normal serum calcium levels. The sensitivity of the parathyroid glands of the PT-VDR−/− mice to calcium was intact as measured by serum PTH levels after changes in serum calcium. This indicates that the reduced CaR in the PT-VDR−/− mice enables a physiologic response to serum calcium. Serum C-terminal collagen crosslinks, a marker of bone resorption, were increased in the PT-VDR−/− mice with no change in the bone formation marker, serum osteocalcin, consistent with a resorptive effect due to the increased serum PTH levels in the PT-VDR−/− mice. Therefore, deletion of the VDR specifically in the parathyroid decreases parathyroid CaR expression and only moderately increases basal PTH levels, suggesting that the VDR has a limited role in parathyroid physiology.

Effects of serum calcium and phosphorus on skeletal mineralization in vitamin D-deficient rats

1986 ◽  
Vol 251 (2) ◽  
pp. E234-E240 ◽  
Author(s):  
M. E. Holtrop ◽  
K. A. Cox ◽  
D. L. Carnes ◽  
M. F. Holick
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Volume Density ◽  
Normal Serum ◽  
Serum Phosphorus ◽  
Deficient Diet ◽  
Hydroxyvitamin D ◽  
Normal Serum Calcium ◽  
Calcium And Phosphorus ◽  
Low Serum

In the present study, we have evaluated the role of calcium and phosphorus concentrations in serum on the mineralization of bone in the absence of vitamin D. This was accomplished by feeding mother rats and subsequently their pups vitamin D-deficient diets varying in calcium, phosphorus, and lactose content. After 5-7 wk on these diets, serum concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-hydroxyvitamin D [1,25(OH)2D] were undetectable. Rats fed a vitamin D-deficient diet containing 0.44% calcium and 0.3% phosphorus showed a serum calcium of 4.9-5.9 mg/dl and a serum phosphorus of 7.3-8.2 mg/dl; rickets (wide epiphysial plates) had developed as well as osteomalacia (wide osteoid seams). Rats maintained on a vitamin D-deficient diet containing 3% calcium and 0.65% phosphorus had normal serum calcium, low serum phosphorus, and severe rickets, but osteomalacia was not seen. Rats fed a diet containing 20% lactose, 4% calcium, and 1% phosphorus showed normal serum calcium, somewhat low serum phosphorus, normal serum PTH, normal width of the epiphysial plate, normal volume density of trabecular bone, and normal volume density of osteoid seams. These data confirm the findings of others, using a different experimental model, that serum calcium and phosphorus concentrations are the determining factors in mineralization defects and not the absence of 25(OH)D or 1,25(OH)2D. In these rats thyroparathyroidectomy is well tolerated, which makes for an ideal model for the study of the effects of calcium-regulating hormones on bone histology, cytology, and biochemistry.

Is Intact PTH a Sensitive Biochemical Indicator of Deranged Calcium Homeostasis in Vitamin D Deficiency?

1989 ◽  
Vol 26 (4) ◽  
pp. 324-327 ◽  
Author(s):  
J P Ashby ◽  
D J Newman ◽  
M G Rinsler
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Calcium Homeostasis ◽  
Biochemical Parameters ◽  
Normal Serum ◽  
Intact Pth ◽  
Hydroxyvitamin D ◽  
Biochemical Indicator ◽  
Normal Serum Calcium ◽  
25 Hydroxyvitamin D

Intact PTH was elevated in 38/40 Asians with reduced serum 25 hydroxyvitamin D [25(OH)D] including seven patients with normal serum calcium, phosphate and alkaline phosphatase. Changes in intact PTH were disproportionately greater than for other biochemical parameters, making it the most sensitive early indicator of deranged calcium homeostasis in vitamin D deficiency.

Relationship Between Nutrient Intake and Vitamin D Status in Osteoporotic Women

2007 ◽  
Vol 77 (6) ◽  
pp. 376-381 ◽  
Author(s):  
de Souza Genaro ◽  
de Paiva Pereira ◽  
de Medeiros Pinheiro ◽  
Szejnfeld ◽  
Araújo Martini
Keyword(s):  
Vitamin D ◽  
Mineral Metabolism ◽  
Sodium Intake ◽  
Serum Vitamin ◽  
Cross Sectional Study ◽  
Dietary Intakes ◽  
Mineral Density ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
Dietary Records

Vitamin D is essential for maintaining calcium homeostasis and optimizing bone health. Its inadequacy is related to many factors including dietary intake. The aim of the present study was to evaluate serum 25(OH)D and its relationship with nutrient intakes in postmenopausal Brazilian women with osteoporosis. This cross-sectional study comprised 45 free-living and assisted elderly at São Paulo Hospital. Three-day dietary records were used to assess dietary intakes. Bone mineral density was measured with a dual-energy X-ray absorptiometer (DXA). Blood and urine sample were collected for analysis of biochemical markers of bone and mineral metabolism. Insufficiency of vitamin D was observed in 24.4% of the women and optimal levels (≥ 50 nmol/L) were observed in 75.6%. Parathyroid hormone was above the reference range in 51% of the participants. The mean calcium (724 mg/day) and vitamin D (4.2 μ g/day) intakes were lower than the value proposed by The Food and Nutrition Board and sodium intake was more than two-fold above the recommendation. Higher levels of serum 25(OH)D were inversely associated with sodium intake. Dietary strategies to improve serum vitamin D must focus on increasing vitamin D intake and should take a reduction of sodium intake into consideration.

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