Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia.
J Bone Miner Metab
; 42(2): 155-165, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38310177
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Osteomalacia
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Raquitismo Hipofosfatêmico Familiar
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Síndrome de Fanconi
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Raquitismo Hipofosfatêmico
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Hipofosfatemia Familiar
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article