Academic Journal
Clinical spectrum and long-term follow-up of non-surgical hypoparathyroidism with novel AIRE and GATA3 variants from India.
| Τίτλος: | Clinical spectrum and long-term follow-up of non-surgical hypoparathyroidism with novel AIRE and GATA3 variants from India. |
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| Συγγραφείς: | Qadir A; Department of General Medicine, Kashmir Medical College, Srinagar, India., Ganie SA; Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India., Misgar RA; Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. drreyaz2017@gmail.com., Chhabra A; Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India., Wani AI; Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India., Bashir MI; Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. |
| Πηγή: | Endocrine [Endocrine] 2026 Aug 06; Vol. 91 (1). Date of Electronic Publication: 2026 Aug 06. |
| Τύπος έκδοσης: | Journal Article; Observational Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Humana Press Country of Publication: United States NLM ID: 9434444 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-0100 (Electronic) Linking ISSN: 1355008X NLM ISO Abbreviation: Endocrine Subsets: MEDLINE |
| Imprint Name(s): | Publication: Feb. 1996- : Totowa, NJ : Humana Press Original Publication: Houndsmills, Basingstoke, Hants, UK : Macmillan Press, c1994- |
| Ιατρικοί όροι (MeSH): | Hypoparathyroidism*/genetics , Hypoparathyroidism*/complications , GATA3 Transcription Factor*/genetics , Transcription Factors*/genetics, Calcium/blood ; Hypocalcemia/genetics ; Humans ; Adolescent ; Female ; Male ; Child ; Child, Preschool ; Infant ; Adult ; AIRE Protein ; Follow-Up Studies ; Young Adult ; India ; Middle Aged ; Mutation |
| Περίληψη: | Purpose: Non-surgical hypoparathyroidism is a rare endocrine disorder associated with substantial long-term morbidity, with limited data from low- and middle-income countries. Materials and Methods: This single-centre ambispective observational cohort study included 27 patients with non-surgical hypoparathyroidism evaluated at a University Hospital between 2013 and 2025. Clinical manifestations, biochemical parameters, treatment requirements, complications, and outcomes were prospectively recorded. Patients with syndromic features underwent whole-exome sequencing. Results: The median age at presentation was 16 years (range 1-60), with a mean follow-up of 6.9 ± 2.9 years. Neuromuscular manifestations of hypocalcaemia were the most frequent presenting features. Severe hypocalcaemia was observed in 23(85.2%) of patients, with inappropriately low parathyroid hormone levels in all cases. Conventional therapy significantly improved mean serum calcium concentrations to 7.95 ± 0.59 mg/dL. Basal ganglia calcification was detected in 15(55.6%), cataracts in 7 (25.9%), QT prolongation in 5(18.5%), and nephrocalcinosis in 4(14.8%). Four patients had syndromic hypoparathyroidism. Genetic analysis identified a novel homozygous splice-site variant in AIRE (c.308-1G > C), a novel frameshift heterozygous AIRE variant (c.758_771del; p.Lys253SerfsTer13), and a novel heterozygous frameshift duplication in GATA3 (c.159dup; p.Asp54Argfs*250). Calcium dose correlated positively with 24-hour urinary calcium excretion (ρ = 0.59, p = 0.002) and nephrocalcinosis (ρ = 0.45, p = 0.018). Conclusion: Non-surgical hypoparathyroidism is associated with significant long-term neurological and renal complications. Renal morbidity is primarily related to treatment intensity and hypercalciuria, whereas extra-renal manifestations appear independent of urinary calcium losses. Identification of novel AIRE and GATA3 mutations expanded the genetic spectrum of syndromic hypoparathyroidism in Indian patients. (© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki (1964) and its subsequent amendments, and with the proper IEC/SKIMS protocol RP 200/2022 dated 28th October, 2022. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Consent to publish has been received from all participants in the study. Conflict of interests: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: AIRE; GATA3; HDR; Hypoparathyroidism; Novel; Syndromic |
| Substance Nomenclature: | 0 (GATA3 Transcription Factor) 0 (GATA3 protein, human) 0 (AIRE Protein) 0 (Transcription Factors) SY7Q814VUP (Calcium) |
| Entry Date(s): | Date Created: 20260806 Date Completed: 20260806 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s12020-026-04731-3 |
| PMID: | 42560401 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1559-0100 |
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| DOI: | 10.1007/s12020-026-04731-3 |