Autosomal Dominant Hypophosphatemic Rickets Presenting in a Phenotypically Normal Adult Female

Area of Science:

• Endocrinology
• Genetics
• Bone Metabolism

Background:

• Autosomal Dominant Hypophosphatemic Rickets (ADHR) is a rare genetic disorder characterized by renal phosphate wasting and hypophosphatemia.
• It is typically caused by mutations in the FGF23 gene, leading to excess fibroblast growth factor 23 (FGF23).
• ADHR often presents in childhood or adolescence, but adult-onset cases can occur.

Observation:

• A 22-year-old female presented with proximal muscle pain, weakness, and insufficiency fractures.
• Initial investigations revealed hypophosphatemia, low 25-hydroxyvitamin D, and elevated FGF23, suggesting osteomalacia and a phosphate-wasting disorder.
• Extensive imaging ruled out tumor-induced osteomalacia.

Findings:

• Genetic testing identified a missense variant in the FGF23 gene, confirming the diagnosis of ADHR.
• A retrospective family history revealed affected relatives with 'bone disorder' and wheelchair dependence.
• Treatment with vitamin D, calcitriol, and phosphate led to complete symptom resolution and normalization of laboratory values.

Implications:

• This case highlights the importance of considering ADHR in adult patients with unexplained hypophosphatemia and bone pain, even with a negative family history.
• Genetic testing for FGF23 mutations is crucial for accurate diagnosis.
• Timely diagnosis and appropriate treatment can effectively manage ADHR symptoms and prevent skeletal complications.