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04.02.2024 | Original Article

Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia

verfasst von: Divya C. Ragate, Saba Samad Memon, Manjiri Karlekar, Anurag Ranjan Lila, Vijaya Sarathi, Tukaram Jamale, Sayali Thakare, Virendra A. Patil, Nalini S. Shah, Tushar R. Bandgar

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 2/2024

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Abstract

Introduction

Fanconi renotubular syndromes (FRTS) are a rare group of inherited phosphaturic disorders with limited Indian as well as global data on this condition. Here, we describe the experience of a single Endocrinology center from Western India on FRTS.

Materials and methods

Comprehensive clinical, biochemical, radiological, management, and genetic details of FRTS patients managed between 2010 and 2023 were collected and analyzed.

Results

FRTS probands had mutations (eight novel) in six genes [CLCN5 (n = 4), SLC2A2 (n = 2), GATM, EHHADH, HNF4A, and OCRL (1 each)]. Among 15 FRTS patients (11 families), rickets/osteomalacia was the most common (n = 14) presentation with wide inter- and intra-familial phenotypic variability. Delayed diagnosis (median: 8.8 years), initial misdiagnosis (8/11 probands), and syndrome-specific discriminatory features (8/11 probands) were commonly seen. Hypophosphatemia, elevated alkaline phosphatase, normal parathyroid hormone (median: 36 pg/ml), high-normal/elevated 1,25(OH)₂D (median: 152 pg/ml), hypercalciuria (median spot urinary calcium to creatinine ratio: 0.32), and variable proximal tubular dysfunction(s) were observed. Elevated C-terminal fibroblast growth factor 23 in two probands was misleading, till the genetic diagnosis was reached. Novel observations in our FRTS cohort were preserved renal function (till sixth decade) and enthesopathy in FRTS1 and FRTS3 families, respectively.

Conclusion

Our findings underscore frequent under- and misdiagnosis of FRTS; hence, a high index of suspicion for FRTS in phosphopenic rickets/osteomalacia, with early consideration of genetic testing is essential to ensure timely diagnosis of FRTS. The novel variants and phenotypic manifestations described here expand the disease spectrum of FRTS.

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Titel: Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia
verfasst von: Divya C. Ragate
Saba Samad Memon
Manjiri Karlekar
Anurag Ranjan Lila
Vijaya Sarathi
Tukaram Jamale
Sayali Thakare
Virendra A. Patil
Nalini S. Shah
Tushar R. Bandgar
Publikationsdatum: 04.02.2024
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 2/2024
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-023-01490-3

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Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia