Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function <i>VDR</i> mutation

Faiyaz-Ul-Haque, Muhammad; AlDhalaan, Waheeb; Al-Ashwal, Abdullah A.; Bin-Abbas, Bassam; Alsagheir, Afaf; Al‐Otaiby, Maram; Rafiq, Zulqurnain; Zaidi, Syed Hassan Ejaz

doi:10.1515/jpem-2017-0312

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…The clinical characteristics, biochemical findings, and responses to therapy of our patients are comparable to those described in the literature [5] and are delineated in Tables I and II. All 8 of our patients presented with growth failure.…”

Section: Discussionsupporting

confidence: 75%

“…The HVDRR is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene. The prevalence of HVDRR is extremely rare, and only around 100 cases are reported in the literature, mostly from regions and countries where interfamily and consanguineous marriages are common (Middle East, Turkey, and Iran) [4][5][6]. Usually, heterozygous mutations in the VDR gene (in parents of affected children) do not cause signs and symptoms of rickets; however, a few cases have been reported of autosomal dominant mutations resulting in clinical manifestations similar to those of HVDRR [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy

Ahmad,

Ansari,

Aleysae

et al. 2024

pedm

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Introduction: Hereditary vitamin D resistant rickets (HVDRR) is a rare autosomal recessive disorder marked by end-organ resistance of 1,25-dihydroxyvitamin D secondary to various mutations in the vitamin D receptor gene. The currently accepted treatment modality involves bypassing the affected receptors in the gut with high-dose intravenous calcium. In a few limited case reports, cinacalcet, a calcimimetic, has been used as an adjunctive therapy. Material and methods: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation. Results: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels. Conclusion:This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy

Ahmad,

Ansari,

Aleysae

et al. 2024

pedm

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“…In the Arab countries, nutritional rickets is still prevalent, 6 7 8 raising the possibility that rare forms of rickets, such as XLHR, may be misdiagnosed as nutritional rickets. This may lead to inappropriate treatment, which could aggravate skeletal deformities making it a challenge to rectify with late treatment.…”

Section: Introductionmentioning

confidence: 99%

“…4 However, recently, a recombinant human immunoglobulin G1 monoclonal antibody targeting FGF-23, burosumab has been approved as a specific therapy for XLHR with promising short-term results. 5 In the Arab countries, nutritional rickets is still prevalent, [6][7][8] raising the possibility that rare forms of rickets, such as XLHR, may be misdiagnosed as nutritional rickets. This may lead to inappropriate treatment, which could aggravate skeletal deformities making it a challenge to rectify with late treatment.…”

Section: Introductionmentioning

confidence: 99%

X-linked Hypophosphatemic Rickets: Awareness, Knowledge, and Practice of Pediatric Endocrinologists in Arab Countries

et al. 2020

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X-linked hypophosphatemic rickets (XLHR) is a genetic disease caused by inactivating pathogenic variants in PHEX, which results in reduced mineralization of bone, teeth, and renal phosphate wasting. XLHR is traditionally treated by phosphate and vitamin D analogs. Recently, burosumab, a recombinant anti-fibroblast growth factor-23 (FGF-23) monoclonal antibody was approved as specific XLHR therapy. We aimed to assess the awareness, knowledge, and management of XLHR among members of the Arab Society for Pediatric Endocrinology and Diabetes (ASPED). Of the 97 physicians who answered the online questionnaire, 97% were aware of XLHR, and while 90% screen family members of the index case, only 29% manage children with XLHR. In children with rickets, 40% of participants measure serum/urine phosphate routinely, and 31% request serum FGF-23 in suspected XLHR cases. Almost all responders use conventional XLHR therapy, and 4% used Burosomab. Only 14% were satisfied with the conventional treatment, and 69% reported therapeutic complications in up to 25% of their patients. Multidisciplinary care for XLHR is practiced by 94%, but 82% of providers did not have transition clinics. Pediatric endocrinologists in ASPED countries are aware of XLHR but have variable practice and are unsatisfied with its conventional treatment. Raising awareness of the recognition and modern management of XLHR is needed.

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“…Vitamin D regulates blood calcium and phosphate concentrations, playing a key role in bone growth and remodeling. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor to regulate the expression of target genes [5]. Vitamin D-resistant rickets of X-linked dominant transmission type is caused by pathology of renal tubular apparatus [14], resulting in impaired absorption of calcium and phosphorus in the small intestine; it belongs to the group of hereditary tubulopathies, clinical picture of which mimics rickets at early stage of the disease, but it is not associated with vitamin D deficiency; it belongs to rare metabolic bone diseases, the pathologies with bone metabolism disorders, majority of which combines various degrees of damage to the skeletal system, teeth and periodontium in general [19].…”

Section: Introductionmentioning

confidence: 99%

Pathological Processes in Oral Cavity at Vitamin D-Resistant Rickets (Family Case Reports)

Japaridze¹

2022

MIMM

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Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation

Abstract: The study concludes that VDR sequencing and laboratory tests are essential to confirm HVDRR and to assess the effectiveness of the treatment.

Cited by 9 publications

References 20 publications

Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy

Hereditary vitamin D resistant rickets (HVDRR) case series: phenotype, genotype, conventional treatment, and adjunctive cinacalcet therapy

X-linked Hypophosphatemic Rickets: Awareness, Knowledge, and Practice of Pediatric Endocrinologists in Arab Countries

Pathological Processes in Oral Cavity at Vitamin D-Resistant Rickets (Family Case Reports)

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