Different Mechanisms of Intestinal Calcium Absorption at Different Life Stages: Therapeutic Implications and Long-Term Responses to Treatment in Patients with Hereditary Vitamin D-Resistant Rickets

Chaturvedi, Deepti; Garabédian, M; Carel, Jean‐Claude; Léger, Juliane

doi:10.1159/000341405

Cited by 14 publications

(10 citation statements)

References 40 publications

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“…82 As described by Fudge and Kovacs, 83 vitamin D receptor-independent mechanisms of intestinal calcium absorption are operative in the placenta and thus may supply normal calcium to the fetus because mineral metabolism is apparently normal at birth in HVDRR infants. 82 As has been noticed in multiple cases of HVDRR, as the affected children grow up, their requirement for calcium supplementation diminishes and calcium can even be discontinued with continued normal mineral metabolism, suggesting that an adaptation occurs with a transition to a VDR-independent pathway to regulate intestinal calcium absorption. One possible explanation is a role for estrogens, which have been shown to upregulate calcium transporter genes by VDR-independent mechanisms.…”

Section: On Calcium and Bonementioning

confidence: 99%

“…This phenomenon occurs around the time of puberty or even before. In a recent paper Chaturvedi et al 82 described the clinical course of three children with the previously reported Arg73X mutation leading to an early truncation in the VDR. The authors detail their findings and support the idea that VDR-independent pathways become operative as children grow up.…”

Section: On Calcium and Bonementioning

confidence: 99%

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Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets

2014

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Heterogeneous loss of function mutations in the vitamin D receptor (VDR) interfere with vitamin D signaling and cause hereditary vitamin D-resistant rickets (HVDRR). HVDRR is characterized by hypocalcemia, secondary hyperparathyroidism and severe early-onset rickets in infancy and is often associated with consanguinity. Affected children may also exhibit alopecia of the scalp and total body. The children usually fail to respond to treatment with calcitriol; in fact, their endogenous levels are often very elevated. Successful treatment requires reversal of hypocalcemia and secondary hyperparathyroidism and is usually accomplished by administration of high doses of calcium given either intravenously or sometimes orally to bypass the intestinal defect in VDR signaling.

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Section: On Calcium and Bonementioning

confidence: 99%

Section: On Calcium and Bonementioning

confidence: 99%

Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets

2014

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“…Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-(OH)2D [3] . IV calcium therapy bypasses the calcium absorption defect in the intestine caused by the lack of action of the mutant VDR [1,18] . However, IV calcium therapy requires a central catheter and prolonged hospitalization.…”

Section: Discussionmentioning

confidence: 99%

“…During childhood, after parenteral calcium treatment to bypass intestinal calcium absorption, it is possible to maintain normal bone through long-term oral calcium supplementation [18] . In our study, 6 patients have been managed with intermittent IV calcium regimens via the peripheral route once a week using high-dose oral calcium in between periods of IV infusion.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characterization of Tunisian Children with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets

Ameur

Silve²,

Chabchoub³

et al. 2016

Horm Res Paediatr

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Background: Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disorder characterized by the early onset of rickets and is caused by mutations in the vitamin D receptor (VDR) gene. Some HVDRR patients also have alopecia. Patients and Methods: We retrospectively studied the clinical features, laboratory findings, genetic defects, as well as responses to treatment in a series of children with HVDRR. Results: Eight patients from 7 families met the inclusion criteria. Alopecia was noted in 7 patients. Two different homozygous mutations in the VDR gene were identified in 6 patients: the p.K45E mutation located in the DNA-binding domain (5 patients with alopecia) and a novel p.T415R mutation located in the ligand-binding domain. A p.E143del CYP24A1 mutation, in the gene encoding the 25-hydroxyvitamin D3-24-hydroxylase, was identified in 2 brothers carrying the VDR gene mutation p.K45E. Six patients were treated with intermittent intravenous calcium treatment via the peripheral route with a clear improvement in 5 cases. Conclusion: To the best of our knowledge, this is the first major series reporting on HVDRR in Tunisia. The same mutation (p.K45E) was found in 5 apparently unrelated affected individuals. We have also extended the mutation spectrum by studying 1 novel VDR mutation.

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“…therapy, with healing of the rickets and reversal of secondary hyperparathyroidism and hypophosphatemia. The suppression of hyperparathyroidism with calcium supplementation alone indicates that the major defect in HVDRR is an inability to absorb calcium in the gastrointestinal tract [1,9,14]. …”

Section: Discussionmentioning

confidence: 99%

Successful Intermittent Intravenous Calcium Treatment via the Peripheral Route in a Patient with Hereditary Vitamin D-Resistant Rickets and Alopecia

Ersoy

Kiremitçi²,

Isojima³

et al. 2015

Horm Res Paediatr

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Background: Hereditary vitamin D-resistant rickets (HVDRR) is a rare genetic disorder caused by mutations in the vitamin D receptor (VDR) gene, which result in end-organ resistance to 1,25-(OH)₂D₃. Patients with HVDRR are mostly treated using i.v. calcium therapy with a central catheter. However, central catheter-related complications have been reported. Patient: The patient was a 3-year-old boy presenting with waddling gait and alopecia. He had hypocalcemia [8 mg/dl (2 mmol/l)], hyperparathyroidism (1,232 ng/l), and elevated 1,25-(OH)₂D₃ levels (>250 pmol/l). DNA sequence analyses of the VDR gene showed a homozygous C-T transition at codon 152, resulting in a non-sense mutation in exon 5. Interventions and Outcomes: The patient was initially treated with calcitriol (80 ng/kg/day) and high-dose oral calcium (150 mg/kg/day) for one year. At the end of the first year, intermittent (5 days per month) i.v. calcium therapy without a central catheter was initiated because of insufficient clinical and radiological improvement. After 2 years of intermittent i.v. calcium therapy, there was a clear improvement based on clinical progress and on X-ray and biochemical findings. No peripheral complications were reported either. Conclusion: HVDRR with a non-sense mutation in the ligand-binding domain and alopecia was successfully treated with intermittent i.v. calcium without a central catheter.

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Different Mechanisms of Intestinal Calcium Absorption at Different Life Stages: Therapeutic Implications and Long-Term Responses to Treatment in Patients with Hereditary Vitamin D-Resistant Rickets

Cited by 14 publications

References 40 publications

Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets

Mutations in the vitamin D receptor and hereditary vitamin D-resistant rickets

Clinical and Genetic Characterization of Tunisian Children with Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets

Successful Intermittent Intravenous Calcium Treatment via the Peripheral Route in a Patient with Hereditary Vitamin D-Resistant Rickets and Alopecia

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