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Published in: Calcified Tissue International 2/2024

19-11-2023 | Rickets | Original Research

Hereditary Hypophosphatemic Rickets with Hypercalciuria Presenting with Enthesopathy, Renal Cysts, and High Serum c-Terminal FGF23: Single-Center Experience and Systematic Review

Authors: Manjunath Havalappa Dodamani, Saba Samad Memon, Manjiri Karlekar, Anurag Ranjan Lila, Mustafa Khan, Vijaya Sarathi, Sneha Arya, Tukaram Jamale, Sayali Thakare, Virendra A. Patil, Nalini S. Shah, Clemens Bergwitz, Tushar R. Bandgar

Published in: Calcified Tissue International | Issue 2/2024

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Abstract

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of phosphate homeostasis. We describe a single-center experience of genetically proven HHRH families and perform systematic review phenotype-genotype correlation in reported biallelic probands and their monoallelic relatives. Detailed clinical, biochemical, radiological, and genetic data were retrieved from our center and a systematic review of Pub-Med and Embase databases for patients and relatives who were genetically proven. Total of nine subjects (probands:5) carrying biallelic SLC34A3 mutations (novel:2) from our center had a spectrum from rickets/osteomalacia to normal BMD, with hypophosphatemia and hypercalciuria in all. We describe the first case of genetically proven HHRH with enthesopathy. Elevated FGF23 in another patient with hypophosphatemia, iron deficiency anemia, and noncirrhotic periportal fibrosis led to initial misdiagnosis as tumoral osteomalacia. On systematic review of 58 probands (with biallelic SLC34A3 mutations; 35 males), early-onset HHRH and renal calcification were present in ~ 70% and late-onset HHRH in 10%. c.575C > T p.(Ser192Leu) variant occurred in 53% of probands without skeletal involvement. Among 110 relatives harboring monoallelic SLC34A3 mutation at median age 38 years, renal calcification, hypophosphatemia, high 1,25(OH)2D, and hypercalciuria were observed in ~30%, 22.3%, 40%, and 38.8%, respectively. Renal calcifications correlated with age but were similar across truncating and non-truncating variants. Although most relatives were asymptomatic for bone involvement, 6/12(50%) had low bone mineral density. We describe the first monocentric HHRH case series from India with varied phenotypes. In a systematic review, frequent renal calcifications and low BMD in relatives with monoallelic variants (HHRH trait) merit identification.
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Literature
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Metadata
Title
Hereditary Hypophosphatemic Rickets with Hypercalciuria Presenting with Enthesopathy, Renal Cysts, and High Serum c-Terminal FGF23: Single-Center Experience and Systematic Review
Authors
Manjunath Havalappa Dodamani
Saba Samad Memon
Manjiri Karlekar
Anurag Ranjan Lila
Mustafa Khan
Vijaya Sarathi
Sneha Arya
Tukaram Jamale
Sayali Thakare
Virendra A. Patil
Nalini S. Shah
Clemens Bergwitz
Tushar R. Bandgar
Publication date
19-11-2023
Publisher
Springer US
Published in
Calcified Tissue International / Issue 2/2024
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-023-01156-2

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