Late onset autosomal dominant hypophosphatemic rickets; confirmation of the diagnosis with genomic analysis

2013 ◽  
Author(s):  
Symeon Tournis ◽  
Ioannis Stathopoulos ◽  
Kalliopi Lampropoulou-Adamidou ◽  
Theodora Koromila ◽  
Nikolaos Chatzistamatas ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Late Onset ◽  
Genomic Analysis ◽  
Hypophosphatemic Rickets ◽  
Autosomal Dominant Hypophosphatemic Rickets

scholarly journals Autosomal Dominant Hypophosphatemic Rickets: A Case Report and Review of the Literature

2021 ◽  
Vol 18 (16) ◽  
pp. 8771
Author(s):  
Chiara Mameli ◽  
Arianna Sangiorgio ◽  
Valeria Colombo ◽  
Mirko Gambino ◽  
Luigina Spaccini ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Late Onset ◽  
Fibroblast Growth Factor 23 ◽  
Failure To Thrive ◽  
Spontaneous Remission ◽  
Hypophosphatemic Rickets ◽  
Autosomal Dominant Hypophosphatemic Rickets ◽  
Heterozygous Variant ◽  
Tubular Phosphate Reabsorption ◽  
Phosphate Salts

Autosomal dominant hypophosphatemic rickets (ADHR) is an extremely rare form of genetic rickets caused by mutations in the fibroblast growth factor 23 gene. ADHR is characterized by hypophosphatemia secondary to isolated renal phosphate wasting. Only a few cases of ADHR have been reported in the literature to date. We describe the case of a 17-month-old girl who presented with severe failure to thrive (length: −4.08 standard deviation (SD), weight: −2.2 SD) and hypotonia. Hypophosphatemia, decreased tubular phosphate reabsorption (69%), and rachitic lesions were found. Genetic analysis showed the heterozygous variant c.536G>A (NM_020638.3:c.536G>A) in exon 3 of the FGF23 gene, leading to the diagnosis of ADHR. She was treated with phosphate salts and oral alfacalcidol. After 4 years of treatment, at 5 years of age, the patient’s ADHR resolved spontaneously. Considering the lack of knowledge regarding ADHR, we reviewed the literature to describe the features of this rare and poorly understood disease. Eleven ADHR pediatric cases have been described thus far, with cases tending to be more common in females than males. Similar to the general population, two groups of patients with ADHR can be described depending on the mutations present: patients with an R179 and R176 mutation have early-onset of disease and higher frequency of rickets, and a milder and late-onset of disease, respectively. Symptoms and disease severity may fluctuate. Spontaneous remission may occur during the pediatric age.

scholarly journals The Autosomal Dominant Hypophosphatemic Rickets (ADHR) Gene Is a Secreted Polypeptide Overexpressed by Tumors that Cause Phosphate Wasting

2001 ◽  
Vol 86 (2) ◽  
pp. 497-500 ◽  
Author(s):  
Kenneth E. White ◽  
Kenneth B. Jonsson ◽  
Gwenaelle Carn ◽  
Geeta Hampson ◽  
Tim D. Spector ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Hypophosphatemic Rickets ◽  
Autosomal Dominant Hypophosphatemic Rickets

scholarly journals Iron Modifies Plasma FGF23 Differently in Autosomal Dominant Hypophosphatemic Rickets and Healthy Humans

2011 ◽  
Vol 96 (11) ◽  
pp. 3541-3549 ◽  
Author(s):  
Erik A. Imel ◽  
Munro Peacock ◽  
Amie K. Gray ◽  
Leah R. Padgett ◽  
Siu L. Hui ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Hypophosphatemic Rickets ◽  
Healthy Humans ◽  
Autosomal Dominant Hypophosphatemic Rickets

An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation

2009 ◽  
Vol 28 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Moez Gribaa ◽  
Mohamed Younes ◽  
Yosra Bouyacoub ◽  
Wided Korbaa ◽  
Ilhem Ben Charfeddine ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Autosomal Dominant ◽  
Hypophosphatemic Rickets ◽  
Autosomal Dominant Hypophosphatemic Rickets ◽  
Tunisian Family

scholarly journals SAT-056 Autosomal Dominant Hypophosphatemic Rickets in Premature Twins Resolved with Iron Supplementation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Guido Alarcon ◽  
Joshua Tarkoff ◽  
Alejandro Diaz
Keyword(s):  
Alkaline Phosphatase ◽  
Iron Supplementation ◽  
Autosomal Dominant ◽  
Iron Status ◽  
Hypophosphatemic Rickets ◽  
Heterozygous Mutation ◽  
Iron Level ◽  
Normal Limits ◽  
Autosomal Dominant Hypophosphatemic Rickets ◽  
Nicu Admission

Abstract Introduction Autosomal dominant hypophosphatemic rickets (ADHR) is a condition with variable phenotype in terms of age of presentation, severity, and possible resolution. ADHR is caused by mutations of FGF23, preventing its cleavage, producing high levels of FGF23, which leads to renal phosphate wasting. Studies in mice and adult humans, have shown a correlation between low iron levels and increased FGF23 levels. To our knowledge, three pediatric patients with ADHR resolved with iron supplementation have been reported in the literature. Clinical case We report on identical twins born at 28 weeks and 5 days by cesarean section due to premature rupture of membranes with complicated pregnancy due to twin-to-twin transfusion syndrome. Birth weights were 780 grams (2nd percentile) for twin A, 1,200 grams (50th percentile) for twin B. Hypophosphatemia was documented starting at 2 weeks of life and during the first 6 of months of life, with phosphorus levels between 2.9-3.9 mg/dL for twin A and between 2.4-5.1 mg/dL for twin B. During their NICU admission phosphorus had a positive relationship with the hemoglobin level, which was more severe on twin A. Both were treated with calcitriol and a low dose of phosphorus starting on their 2nd month of life. At 6 months of age, both had persistent hypophosphatemia, more prominently in twin A (2.7mg/dL) with high alkaline phosphatase (1,209 IU/L) and high FGF23 (343 RU/dL). At that time his hemoglobin was 9.8 g/dL and his hematocrit was 29.5%. Both were started on Polyvisol with iron. At 14 months of life phosphorus and calcium were within normal limits, therefore calcitriol and phosphate were discontinued. At 15 months of age their hemoglobin, hematocrit, iron level, and TIBC levels were normal for both twins. Phosphorus was 4.6 and 4.3 mg/dL, alkaline phosphatase reduced significantly to 819 and 413IU/L, and FGF23 normalized to 100 RU/dL and 32 RU/dL on twin A and B respectively. Upon physical examination at 15 months of age, twin A was at the 0.02% for length and weight/length at the 31%; twin B was at the 5% for length and weight/length at the 50%. Both twins had high arched palates. Twin A had craniosynostosis, left renal agenesis, bilateral epicanthal folds, overlapping 2nd toes, and clinodactyly of the fifth digits. Note the donor kid (twin A) had a more severe presentation. Genetic testing showed heterozygous mutation c536G>a (p.Arg179GLN) in the FGF23 gene. This is the same mutation previously reported to be related with ADHR resolved with iron supplementation Conclusion The study of patients with hypophosphatemia and hypophosphaturia should include evaluation of iron status (ferritin, TIBC). Treating iron deficiency on these patients might normalize phosphate levels. This would avoid cumbersome treatment with phosphate and calcitriol. Laboratory values Phosphorus:4-8 mg/dL Alkaline Phosphatase: 130-317 IU/L FGF23: 44-215 RU/dL

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