The Variant p.Ala84Pro Is Causative of X-Linked Hypophosphatemic Rickets: Possible Relationship with Burosumab Swinging Response in Adults

Loss of function mutations in the gene could determine X-linked dominant hypophosphatemia. This is the most common form of genetic rickets. It is characterized by renal phosphate wasting determining an increase in fibroblast growth factor 23 (FGF-23), growth retard, bone deformities and musculoskele...

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Published in:Genes 2023-01, Vol.14 (1), p.80
Main Authors: Zagari, Maria Carmela, Chiarello, Paola, Iuliano, Stefano, D'Antona, Lucia, Rocca, Valentina, Colao, Emma, Perrotti, Nicola, Greco, Francesca, Iuliano, Rodolfo, Aversa, Antonio
Format: Article
Language:English
Subjects:
Adults
Bone growth
Bone surgery
Case Report
Endocrinology
Familial Hypophosphatemic Rickets - diagnosis
Familial Hypophosphatemic Rickets - drug therapy
Familial Hypophosphatemic Rickets - genetics
FDA approval
Fibroblast growth factor 23
Genotypes
Humans
Hypophosphatemia
Laboratories
Male
Mutation
Pain
Pedigree
Phenotypes
Phosphatase
Phosphates
Phosphorus
Quality of Life
Rickets
Vitamin D
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Summary:Loss of function mutations in the gene could determine X-linked dominant hypophosphatemia. This is the most common form of genetic rickets. It is characterized by renal phosphate wasting determining an increase in fibroblast growth factor 23 (FGF-23), growth retard, bone deformities and musculoskeletal manifestations. In recent decades, analysis of the gene has revealed numerous different mutations. However, no clear genotype-phenotype correlations have been reported in patients with hypophosphatemic rickets (XLH). We report two cases of a 28-year-old-male (patient 1) and a 19-year-old male (patient 2) affected by XLH initially treated with phosphate and 1,25-dihydroxyvitamin-D admitted to the Endocrinology unit because of the persistence of muscle weakness, bone pain and fatigue. After phosphate withdrawal, both patients started therapy with burosumab and symptoms ameliorated in three months. However, patient 1's biochemical parameters did not improve as expected so we decided to investigate his genetic asset. We herein describe a possible clinical implication for the missense "de novo" mutation, c.250G>C (p.Ala84Pro) in the gene, reported in the database and classified as a variant of uncertain significance (VUS). The clinical implication of this mutation on disease burden and quality of life in adults is still under investigation.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14010080