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Genotypic Spectrum and its Correlation with Alopecia and Clinical Response in Hereditary Vitamin D Resistant Rickets: Our Experience and Systematic Review

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Abstract

Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5%) and preceded the onset of rickets. Patients with alopecia had higher serum calcium (7.6 vs.6.9 mg/dl, p = 0.008), lower 1, 25(OH)2 D (200 vs.320 pg/ml, p = 0.03) and similar overall response to oral therapy (28.7% vs. 35.3%, p = 0.56). Alopecia was present in 51.4% of non-truncating (NT) ligand-binding domain (LBD) variants, whereas it was universal in truncating LBD and all DNA binding-domain (DBD) variants. Overall response to oral therapy was highest in LBD-NT (46.4%) as compared to 7.6% in LBD-truncating and 19% in DBD-NT variants. Among LBD-NT variants, those affecting RXR heterodimerization, but not those affecting ligand affinity, were associated with alopecia. Both alopecia and overall response have genotypic correlation. Age at diagnosis and overall response to oral therapy were similar between patients with and without alopecia in genetically proven HVDRR.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgement

We acknowledge Vyankatesh Shivane, Neeta Doiphode, Neelam Jaguste for administrative help.

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Authors and Affiliations

  1. Department of Endocrinology, Seth G.S Medical College & KEM Hospital, Parel, Mumbai, Maharashtra, 4000012, India

    Manjunath Havalappa Dodamani, Anurag Ranjan Lila, Saba Samad Memon, Sneha Arya, Ankita Rane, Manjeet Kaur Sehemby, Robin Garg, Manjiri Karlekar, Virendra A. Patil & Tushar R. Bandgar

  2. Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India

    Vijaya Sarathi

  3. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India

    Vishwambhar Vishnu Bhandare & Ambarish Kunwar

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  1. Manjunath Havalappa Dodamani
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Correspondence to Saba Samad Memon.

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Manjunath Havalappa Dodamani, Anurag Ranjan Lila, Saba Samad Memon, Vijaya Sarathi, Sneha Arya, Ankita Rane, Manjeet Kaur Sehemby, Robin Garg, Vishwambhar Vishnu Bhandare, Manjiri Karlekar, Virendra A Patil, Ambarish Kunwar, Tushar R Bandgar have no conflict of interest to disclose.

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The study was conducted in accordance with the Declaration of Helsinki and weiver of the informed consent was approved by the institutional ethical committe due to retrospective nature of the study.

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Dodamani, M.H., Lila, A.R., Memon, S.S. et al. Genotypic Spectrum and its Correlation with Alopecia and Clinical Response in Hereditary Vitamin D Resistant Rickets: Our Experience and Systematic Review. Calcif Tissue Int 112, 483–492 (2023). https://doi.org/10.1007/s00223-023-01061-8

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