scholarly journals Variable Clinical Presentation of Children With Hereditary Hypophosphatemic Rickets With Hypercalciuria: A Case Series

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A708-A708
Author(s):  
Stephanie Christensen ◽  
Peter J Tebben ◽  
David Sas ◽  
Ana Creo
Keyword(s):  
Vitamin D ◽  
Sodium Phosphate ◽  
Serum Phosphorus ◽  
Hypophosphatemic Rickets ◽  
Urinary Stones ◽  
Dihydroxyvitamin D ◽  
Presenting Symptoms ◽  
Renal Tubular Cells ◽  
1,25 Dihydroxyvitamin D ◽  
Low Serum

Abstract Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a rare condition of phosphate wasting due to variants in the SLC34A3 gene, encoding the sodium-phosphate cotransporter 2c (NaPi2c) at the brush border of proximal renal tubular cells (1). While labs are characterized by low serum phosphorus, high 1,25 dihydroxyvitamin D and inappropriately high levels of urine phosphate and calcium, the presenting symptoms can vary widely. Little remains known about specific phenotype-genotype correlations, especially in children. Clinical Cases: We report three new cases of HHRH in an unrelated 12 year-old male, 9 year-old female and 14 year-old male. All three patients were found to have low serum phosphorus for age (2.9-3.2 mg/dL), normocalcemia (9.4-9.9 mg/dL), low to low-normal parathyroid hormone (7-15 pg/mL), elevated 1,25 dihydroxyvitamin D (91-178 pg/mL), and hypercalciuria (4.5-7.6 mg/kg/day). Urine phosphorus was inappropriately elevated given the degree of their hypophosphatemia. Despite having similar lab findings, however, their clinical presentations were varied. The 12 year-old male presented with lower extremity pain, which was previously ascribed to patellofemoral pain syndrome. He had no history of renal symptoms, though a renal ultrasound later identified stones bilaterally. Conversely, the 9 year-old female and 14 year-old male presented with recurrent urinary stones and no bone symptoms. Genetic analyses identified 4 novel SLC34A3 gene mutations. Of interest, the 12 year-old male and 9 year-old female each shared a variant (c.575C-T (p.Ser192Leu)) despite having disparate symptoms. All three patients were treated with phosphorus supplementation and were advised to discontinue Vitamin D, if this had previously been prescribed. Conclusion: These three cases highlight the variability of presenting signs and symptoms among individuals with HHRH. Obtaining an accurate diagnosis is critical, as the addition of Vitamin D can seriously worsen symptoms in HHRH though it is a commonly used treatment for other disorders of phosphate wasting and bone demineralization. To aid in clinical decision making, we present a stepwise approach to the diagnosis of hypophosphatemic diseases. References: (1) Lorenz-Depiereux, B., Benet-Pages, A., Eckstein, G., Tenenbaum-Rakover, Y., Wagenstaller, J., Tiosano, D., Gershoni-Baruch, R., Albers, N., Lichtner, P., Schnabel, D., Hochberg, Z., Strom, T. Hereditary Hypophosphatemic Rickets with Hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am. J. Hum. Genetic. 2006;78:193-201.

Hypercalciuric Hypophosphatemic Rickets, Mineral Balance, Bone Histomorphometry, and Therapeutic Implications of Hypercalciuria

PEDIATRICS ◽  
1989 ◽  
Vol 84 (2) ◽  
pp. 276-280
Author(s):  
C. Chen ◽  
T. Carpenter ◽  
N. Steg ◽  
R. Baron ◽  
C. Anast
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Hypophosphatemic Rickets ◽  
Balance Study ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Study Results ◽  
Calcium And Phosphorus

A 14-year-old Turkish boy had severe rickets that had been clinically evident since he was 2 years of age. When he was 5 years of age, he had normal serum calcium and phosphorus levels and increased alkaline phosphatase activity. Treatment with modest dosages of vitamin D (5000 U/d for 3 weeks) resulted in hypercalcemia. At 10 years of age, high-dose vitamin D (40 000 U/d) plus phosphorus (1.1 g/d) therapy for 20 days resulted in symptomatic nephrolithiasis. When, 14 years of age, he had normocalcemia, hypophosphatemia, increased alkaline phosphatase activity, and normal circulating parathyroid hormone concentration. Levels of 25-hydroxyvitamin D were normal but those of 1,25-dihydroxyvitamin D were markedly increased. Rickets and osteopenia were evident on radiographs, and osteomalacia was present on trabecular bone obtained at biopsy. Balance study results showed increased intestinal absorption of calcium and phosphorus, hypercalciuria, and increased urinary phosphorus excretion. This patient manifests an unusual form of hypophosphatemic rickets in which hypercalciuria is a cardinal feature. In contrast with most varieties of hypophosphatemia, this disorder is characterized by appropriately increased production of 1,25-dihydroxyvitamin D in response to hypophosphatemia. It is recommended that urinary calcium excretion be assessed in all patients with hypophosphatemic rickets so that appropriate therapy will be instituted.

scholarly journals A case of X-linked hypophosphatemic rickets: complications and the therapeutic use of cinacalcet

2008 ◽  
Vol 159 (suppl_1) ◽  
pp. S101-S105 ◽  
Author(s):  
Helge Ræder ◽  
Nick Shaw ◽  
Coen Netelenbos ◽  
Robert Bjerknes
Keyword(s):  
Vitamin D ◽  
Sodium Phosphate ◽  
Fibroblast Growth Factor 23 ◽  
Normal Growth ◽  
Current Treatment ◽  
Phosphate Transporter ◽  
Hypophosphatemic Rickets ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Bone Deformities

In hypophosphatemic rickets, there are both inherited and acquired forms, where X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the phosphate-regulating endopeptidase (PHEX) gene. XLH is associated with growth retardation and bone deformities. The renal tubular cells have an important role in calcium and phosphate metabolism, where the 1α-hydroxylase enzyme metabolizes the conversion of 25 (OH)-vitamin D to potent 1,25 (OH)2-vitamin D, whereas the sodium–phosphate transporter controls tubular phosphate reabsorption. The pathophysiological defect in XLH is speculated to cause an increase in a circulating phosphate regulating hormone termed phosphatonin (fibroblast growth factor 23 is the primary phosphatonin candidate), which leads to inhibition of 1α-hydroxylase, and simultaneously to inhibition of the sodium–phosphate transporter domain NPT2c leading to parathyroid hormone-independent phosphaturia. Hence, current treatment of XLH is 1,25 (OH)2-vitamin D or the vitamin D analog alfacalcidol and elementary phosphorus. Unfortunately, patients with XLH may develop nephrocalcinosis, secondary or tertiary hyperparathyroidism, and in some situations also hypertension and cardiovascular abnormalities. We describe a patient with XLH caused by a novel missense mutation in the PHEX gene, who on treatment with alfacalcidol and oral phosphate had normal growth and minimal bone deformities, but who subsequently developed moderate nephrocalcinosis, significant hyperparathyroidism, hypercalcemia, renal failure, and hypertension. We also report the use of the calcimimetic drug cinacalcet in the successful treatment of hypercalcemia and hyperparathyroidism.

Letters to the Editor

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 484-484
Author(s):  
James C. M. Chan ◽  
Frederic C. Bartter
Keyword(s):  
Vitamin D ◽  
Growth Velocity ◽  
Hypophosphatemic Rickets ◽  
Distinct Advantage ◽  
Letters To The Editor ◽  
Initial Report ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Accelerated Growth ◽  
Vitamin D Toxicity

In the treatment of renal hypophosphatemic rickets, the risks of hypercalcemia and vitamin D toxicity are always imminent. The use of 1,25-dihydroxyvitamin D with its shorter half-life offers a distinct advantage in conjunction with the continuous phosphate supplementation.1-3 The accelerated growth velocity secondary to the use of 1,25-dihydroxyvitamin D has now been extended to five patients. The initial report in a 3-year-old girl2 showed acceleration of growth velocity from the 25th to the 78th percentile.

scholarly journals Two Vitamin D Response Elements Function in the Rat 1,25-Dihydroxyvitamin D 24-Hydroxylase Promoter

1995 ◽  
Vol 270 (4) ◽  
pp. 1675-1678 ◽  
Author(s):  
Claudia Zierold ◽  
Hisham M. Darwish ◽  
Hector F. DeLuca
Keyword(s):  
Vitamin D ◽  
Response Elements ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

scholarly journals Reduced Kidney Function and Relative Hypocalciuria—Observational, Cross-Sectional, Population-Based Data

2020 ◽  
Vol 9 (12) ◽  
pp. 4133
Author(s):  
Massimo Cirillo ◽  
Giancarlo Bilancio ◽  
Pierpaolo Cavallo ◽  
Francesco Giordano ◽  
Gennaro Iesce ◽  
...  
Keyword(s):  
Kidney Function ◽  
Population Based ◽  
Calcium Handling ◽  
Urine Calcium ◽  
Cross Sectional ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Calcium Load ◽  
Reduced Kidney Function ◽  
Low Serum

This observational, cross-sectional, epidemiological analysis investigated relationships of kidney function to urine calcium and other variables. The analyses targeted two population-based samples of adults (Gubbio study and Moli-sani study: n = 3508 and 955, respectively). Kidney function was assessed as estimated glomerular filtration rate (eGFR). Calcium/creatinine ratio (Ca/Cr) was used as index of urinary calcium in timed overnight urine under fed condition (Gubbio study), morning urine after overnight fast (Gubbio study), and first-void morning urine (Moli-sani study). Moli-sani study included also data for glomerular filtered calcium load, tubular calcium handling, and serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, calcium, and 25-hydroxyvitamin D. eGFR positively and independently related to Ca/Cr (p < 0.001). In multivariate analyses, eGFR lower by 10 mL/min × 1.73 m2 related to overnight urine Ca/Cr lower by 14.0 mg/g in men and 17.8 mg/g in women, to morning urine Ca/Cr lower by 9.3 mg/g in men and 11.2 mg/g in women, and to first-void urine Ca/Cr lower by 7.7 mg/g in men and 9.6 mg/g in women (p < 0.001). eGFR independently related to glomerular filtered calcium load (p < 0.001) and did not relate to tubular calcium handling (p ≥ 0.35). In reduced eGFR only (<90 mL/min × 1.73 m2), low urine Ca/Cr independently related to low serum 1,25-dihydroxyvitamin D (p = 0.002) and did not relate to hyperphosphatemia, high serum parathyroid hormone, or hypocalcemia (p ≥ 0.14). Population-based data indicated consistent associations of lower kidney function with lower urine calcium due to reduction in glomerular filtered calcium. In reduced kidney function, relative hypocalciuria associated with higher prevalence of low serum 1,25-dihydroxyvitamin D.

Measurement of Plasma 1,25 Dihydroxyvitamin D Using a Novel Immunoextraction Technique and Immunoassay with Iodine Labelled Vitamin D Tracer

1997 ◽  
Vol 34 (6) ◽  
pp. 632-637 ◽  
Author(s):  
W D Fraser ◽  
B H Durham ◽  
J L Berry ◽  
E B Mawer
Keyword(s):  
Vitamin D ◽  
Solid Phase ◽  
Plasma Concentrations ◽  
Sample Volume ◽  
Cross Reactivity ◽  
Regression Equations ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
High Concentrations

We evaluated a novel assay for the measurement of 1,25 dihydroxyvitamin D (1,25 (OH)2D). Immunoextraction of 1,25 (OH)2D is performed using a mini column containing a solid-phase monoclonal antibody followed by radioimmunoassay (RIA) using an 125I-labelled 1,25 (OH)2D derivative tracer and Sac-cell separation. The mean recovery of 1,25(OH)2D3 was 101%, linearity was excellent, inter- and intra-assay coefficients of variation were 9, 8 and 13% and 11, 10 and 14% at low, medium and high concentrations of 1,25(OH)2D3, respectively. The cross-reactivity of vitamin D metabolites was <0·0015% for 25-hydroxyvitamin D3, 24, 25 dihydroxyvitamin D3 and dihydrotachysterol and 0·54% for lα calcidol. 1,25 dihydroxyvitamin D2 cross-reactivity was 79%. The detection limit of the assay was 5pmol/L. Comparison with a commercial radio receptor assay (RRA) and an in-house RIA gave regression equations of y = 0·94x+11·8 ( r = 0·98) and y = 0·91x-1·7 ( r = 0.95), respectively, with no major discrepancies between the methods in all patient groups studied. Plasma concentrations of 1,25 (OH)2D obtained with the assay were as follows: normal, unsupplemented subjects: mean 88, range 48–155 pmol/L, n = 68, patients with chronic renal failure: mean 11, range 3–36 pmol/L, n = 27, primary hyperparathyroidism: mean 198, range 130–299 pmol/L, n = 23, Paget's disease: mean 92, range 42–149 pmol/L, n = 24, osteomalacia: mean 43, range 27–61 pmol/L, n = 9. A minimum sample volume of 300 μL is required, the hands-on time is significantly less than other commercial assays and the measuring procedure is gamma counting rather than scintillation counting. The assay offers several advantages over previous methods and should allow more laboratories to offer measurement of 1,25 (OH)2D as part of their repertoire.

scholarly journals Vitamin D Status among Thai School Children and the Association with 1,25-Dihydroxyvitamin D and Parathyroid Hormone Levels

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104825 ◽  
Author(s):  
Lisa A. Houghton ◽  
Andrew R. Gray ◽  
Michelle J. Harper ◽  
Pattanee Winichagoon ◽  
Tippawan Pongcharoen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
School Children ◽  
Vitamin D Status ◽  
Hormone Levels ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

scholarly journals 1,25-Dihydroxyvitamin D3 and Development of Tuberculosis in Cattle

2003 ◽  
Vol 10 (6) ◽  
pp. 1129-1135 ◽  
Author(s):  
S. G. Rhodes ◽  
L. A. Terry ◽  
J. Hope ◽  
R. G. Hewinson ◽  
H. M. Vordermeier
Keyword(s):  
Vitamin D ◽  
T Cell ◽  
Mononuclear Cells ◽  
T Cell Proliferation ◽  
Accessory Cell ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
Cell Responses ◽  
1,25 Dihydroxyvitamin D ◽  
Accessory Cells

ABSTRACT This report describes the presence and activity of 1,25-dihydroxyvitamin D3 (1,25-D3) in experimental bovine tuberculosis. Animals that went on to develop tuberculous lesions exhibited a rapid transient increase in serum 1,25-D3 within the first 2 weeks following infection with Mycobacterium bovis. 1,25-D3-positive mononuclear cells were later identified in all tuberculous granulomas by immunohistochemical staining of postmortem lymph node tissue. These results suggest a role for 1,25-D3 both at the onset of infection and in the development of the granuloma in these infected animals. Using a monoclonal antibody to the vitamin D receptor (VDR) as a VDR agonist, we confirmed that activation of the vitamin D pathway profoundly depresses antigen-specific, but not mitogenic, bovine peripheral blood T-cell responses (proliferation and gamma interferon production). Investigation of the mechanism of this suppression showed that the VDR antibody modified the expression of CD80 by accessory cells, such that a significant positive correlation between T-cell proliferation and accessory cell CD80 emerged.

Seasonal Variation in Serum 25-Hydroxy Vitamin D3 Does Not Affect 1,25-Dihydroxy Vitamin D

1994 ◽  
Vol 31 (1) ◽  
pp. 31-34 ◽  
Author(s):  
T J Hine ◽  
N B Roberts
Keyword(s):  
Vitamin D ◽  
Seasonal Variation ◽  
Reference Range ◽  
Seasonal Pattern ◽  
Individual Variability ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxy Vitamin D ◽  
Time Periods ◽  
Sunlight Hours

The seasonal variation of serum 25-hydroxy vitamin D3 and 1,25-dihydroxyvitamin D has been investigated. Blood was taken from 27 healthy volunteers, aged 21–44 years old at 3 monthly intervals over a period of 1 year. A scrolling monthly programme with 12 quarterly (3 month) time periods was developed. A summer associated increase in 25-hydroxy vitamin D3 was significantly correlated with but lagged behind by 2 months, the increase in recorded sunlight hours. However, four individuals showed no seasonal rise but maintained constant concentrations throughout the year within the established reference range. Serum 1,25-dihydroxy vitamin D showed marked intra-individual variability with no seasonal pattern although the highest concentration (180 pmol/L) was observed in the winter and no concentration greater than 108 pmol/L in the summer.

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