Hypophosphatemic rickets and short stature

Area of Science:

• Pediatric Endocrinology
• Medical Genetics
• Biochemistry

Background:

• A 18-month-old male presented with significant gross motor delay and poor growth, exhibiting radiographic signs of metaphyseal dysplasia and craniosynostosis.
• Biochemical analyses revealed hypophosphatemic rickets characterized by low serum phosphorus, elevated alkaline phosphatase, and renal phosphate wasting.
• Elevated C-terminal fibroblast growth factor 23 (FGF23) levels suggested FGF23-mediated hypophosphatemia.

Purpose of the Study:

• To investigate the underlying cause of hypophosphatemic rickets in a pediatric patient.
• To evaluate the efficacy of iron repletion in managing autosomal dominant hypophosphatemic rickets (ADHR) associated with iron deficiency.
• To assess the impact of normalizing iron levels on clinical and biochemical parameters in a patient with ADHR.

Main Methods:

• Clinical presentation, radiographic findings, and biochemical markers (serum phosphorus, alkaline phosphatase, TmP/GFR, FGF23, ferritin) were assessed.
• Genetic analysis identified a pathogenic variant in the FGF23 gene, confirming autosomal dominant hypophosphatemic rickets (ADHR).
• Treatment involved initial calcitriol and phosphate, followed by oral ferrous sulfate for iron deficiency, with subsequent monitoring of clinical and biochemical outcomes.

Main Results:

• Genetic testing revealed a pathogenic FGF23 variant (c.527G>A) confirming ADHR. Low ferritin levels were noted, consistent with reported associations.
• Following oral ferrous sulfate treatment and normalization of ferritin, significant biochemical improvements were observed: decreased FGF23, normalized phosphorus, and reduced alkaline phosphatase.
• The patient demonstrated improved developmental milestones, linear growth, radiographic normalization of metaphyses, and stabilization of craniosynostosis over three years.

Conclusions:

• This case highlights that autosomal dominant hypophosphatemic rickets (ADHR) can be associated with iron deficiency, impacting clinical presentation and treatment response.
• Normalization of iron levels in ADHR patients with coexisting iron deficiency can lead to substantial biochemical and clinical improvements, potentially allowing discontinuation of other therapies.
• While X-linked hypophosphatemia is common, considering other etiologies like ADHR is crucial for appropriate management, as therapeutic strategies differ significantly.