{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:10:41Z","timestamp":1791951041566,"version":"4.3.4"},"reference-count":20,"publisher":"Walter de Gruyter GmbH","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2021-0403_abs_001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Vitamin D dependent rickets type 1 (VDDR1) is a rare disease due to pathogenic variants in 1-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      hydroxylase gene. We describe our experience with systematic review of world literature to describe phenotype and genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2021-0403_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seven patients from six unrelated families with genetically proven VDDR1 from our cohort and 165 probands from systematic review were analyzed retrospectively. The clinical features, biochemistry, genetics, management, and long-term outcome were retrieved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2021-0403_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In our cohort, the median age at presentation and diagnosis was 11(4\u201318) and 40(30\u2013240) months. The delayed diagnoses were due to misdiagnoses as renal tubular acidosis and hypophosphatemic rickets. Four had hypocalcemic seizures in infancy whereas all had rickets by 2 years. All patients had biochemical response to calcitriol, however two patients diagnosed post-puberty had persistent deformity. Genetic analysis revealed two novel (p.Met260Arg, p.Arg453Leu) and a recurring variant (p.Phe443Profs*24). Systematic review showed that seizures as most common presentation in infancy, whereas delayed motor milestones and deformities after infancy. Diagnosis was delayed in 27 patients. Patients with unsatisfactory response despite compliance were &gt;12 years at treatment initiation. Inappropriately normal 1,25(OH)2D may be present, however suppressed ratio of 1,25(OH)2 D\/25(OH)D may provide a clue to diagnosis. Various region specific and hot-spot recurrent variants are described. Patients with truncating variants had higher daily calcitriol requirement and greatly suppressed ratio of 1,25(OH)2D\/25(OH)D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2021-0403_abs_004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Delayed diagnosis may lead to permanent short stature and deformities. Truncating variants tend to have severe disease as compared to non-truncating variants. Diagnostic accuracy of 1,25(OH)2 D\/25(OH)D ratio needs further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2021-0403","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T17:20:47Z","timestamp":1631035247000},"page":"1505-1513","source":"Crossref","is-referenced-by-count":25,"title":["Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review"],"prefix":"10.1515","volume":"34","author":[{"given":"Manjunath Havalappa","family":"Dodamani","sequence":"first","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjeetkaur","family":"Sehemby","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba Samad","family":"Memon","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya","family":"Sarathi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Vydehi institute of medical sciences and research centre , Bangalore , Karnataka , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag R.","family":"Lila","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Chapla","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Diabetes & Metabolism, Christian Medical College and Hospital , Vellore , Tamilnadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwambhar Vishnu","family":"Bhandare","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering , Indian Institute of Technology Bombay , Mumbai , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virendra A.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalini S.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Diabetes & Metabolism, Christian Medical College and Hospital , Vellore , Tamilnadu , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambarish","family":"Kunwar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering , Indian Institute of Technology Bombay , Mumbai , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar R.","family":"Bandgar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Seth G.S Medical College and KEM Hospital , Mumbai , Maharashtra , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"2022011514413058523_j_jpem-2021-0403_ref_001","doi-asserted-by":"crossref","unstructured":"Wang, JT, Lin, CJ, Burridge, SM, Fu, GK, Labuda, M, Portale, AA, et al.. Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families. Am J Hum Genet 1998;63:1694\u2013702, https:\/\/doi.org\/10.1086\/302156.","DOI":"10.1086\/302156"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_002","doi-asserted-by":"crossref","unstructured":"Kitanaka, S, Takeyama, K, Murayama, A, Sato, T, Okumura, K, Nogami, M, et al.. Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. N Engl J Med 1998;338:653\u201361, https:\/\/doi.org\/10.1056\/nejm199803053381004.","DOI":"10.1056\/NEJM199803053381004"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_003","doi-asserted-by":"crossref","unstructured":"Smith, SJ, Rucka, AK, Berry, JL, Davies, M, Mylchreest, S, Paterson, CR, et al.. Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages. J Bone Miner Res 1999;14:730\u20139, https:\/\/doi.org\/10.1359\/jbmr.1999.14.5.730.","DOI":"10.1359\/jbmr.1999.14.5.730"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_004","doi-asserted-by":"crossref","unstructured":"Miller, WL, Portale, AA. Genetics of vitamin D biosynthesis and its disorders. 2001;15(1):95\u2013109, https:\/\/doi.org\/10.1053\/beem.2001.0122.","DOI":"10.1053\/beem.2001.0122"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_005","doi-asserted-by":"crossref","unstructured":"Kaygusuz, SB, Alavanda, C, Kirkgoz, T, Eltan, M, Yavas Abali, Z, Helvacioglu, D, et al.. Does genotype-phenotype correlation exist in vitamin D-dependent rickets type IA: report of 13 new cases and review of the literature. 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J Clin Invest 1972;51:749\u201359, https:\/\/doi.org\/10.1172\/jci106869.","DOI":"10.1172\/JCI106869"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_013","doi-asserted-by":"crossref","unstructured":"Hulter, HN, Peterson, JC. Acid-base homeostasis during chronic PTH excess in humans. Kidney Int 1985;28:187\u201392, https:\/\/doi.org\/10.1038\/ki.1985.139.","DOI":"10.1038\/ki.1985.139"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_014","doi-asserted-by":"crossref","unstructured":"Emmett, M, Seldin, DW. Disturbances in acid-base balance during hypophosphatemia and phosphate depletion. Adv Exp Med Biol 1978;103:313\u201325, https:\/\/doi.org\/10.1007\/978-1-4684-7758-0_33.","DOI":"10.1007\/978-1-4684-7758-0_33"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_015","doi-asserted-by":"crossref","unstructured":"Wrong, O, Henderson, JE, Kaye, M. Distal renal tubular acidosis: alkali heals osteomalacia and increases net production of 1,25-dihydroxyvitamin D. Nephron Physiol 2005;101:72\u20136, https:\/\/doi.org\/10.1159\/000087537.","DOI":"10.1159\/000087537"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_016","doi-asserted-by":"crossref","unstructured":"Bharati, J, Bhatia, D, Khandelwal, P, Gupta, N, Sinha, A, Khadgawat, R, et al.. C-terminal fibroblast growth factor-23 levels in non-nutritional hypophosphatemic rickets. Indian J Pediatr 2019;86:555\u20137, https:\/\/doi.org\/10.1007\/s12098-019-02909-4.","DOI":"10.1007\/s12098-019-02909-4"},{"key":"2022011514413058523_j_jpem-2021-0403_ref_017","doi-asserted-by":"crossref","unstructured":"Giannakopoulos, A, Efthymiadou, A, Chrysis, D. A case of vitamin-D-dependent rickets type 1A with normal 1,25-dihydroxyvitamin D caused by two novel mutations of the CYP27B1 gene. 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