Endocrine Abstracts

JOINT2832

Background: Bone metabolic conditions causing short stature result from genetic, hormonal, or metabolic abnormalities that impair bone growth and strength. Among them, hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an extremely rare autosomal recessive disorder caused by mutations in the SLC34A3 gene, which encodes for the proximal tubular transporter NaPi-IIc, thus leading to impaired phosphate reabsorption and subsequent hypophosphatemia, hypercalciuria and impaired bone mineralization. The diagnosis can be challenging, particularly when presenting with severe growth impairment. We report a case of HHRH initially suspected as growth hormone deficiency due to short stature and delayed bone age, ultimately leading to an unexpected diagnosis.

Case Presentation: A 10-year-old boy presented with severe short stature (-4.13 SDS), genu varum, and chronic joint pain. He was born at term with a normal birth history, breastfed for 13 months, and had normal psychomotor development. There is no family history of rickets or other metabolic bone disease. Initial evaluation revealed low IGF-1 (105 ng/mL), bone age delayed by 2 years, and an appropriate growth hormone response to arginine stimulation testing, ruling out growth hormone deficiency. Laboratory investigations showed persistent hypophosphatemia (serum phosphate 2.3 mg/dL), with normal levels of serum calcium (9.54 mg/dL) and 25-hydroxyvitamin D (34.89 ng/mL), and elevated alkaline phosphatase (543 U/l). Urinary analysis confirmed hypercalciuria (292 mg/24h) and reduced tubular phosphate reabsorption (TMP/GFR = 0.92 mmol/l). Additionally, 1,25-dihydroxyvitamin D was elevated (126 pg/mL), whereas serum PTH was reduced (8.19 pg/mL) and fibroblast growth factor 23 (FGF23) was undetectable, supporting the diagnosis of HHRH. The radiologic assessment revealed a rickets severity score of 7/10. No images of renal calcifications were found on the abdominal ultrasound.

Conclusion: The biochemical profile—persistent hypophosphatemia, suppressed PTH, hypercalciuria, elevated 1,25-dihydroxyvitamin D, and low FGF23—helped differentiate HHRH from other phosphate-wasting disorders, such as X-linked hypophosphatemia, autosomal dominant/recessive hypophosphatemic rickets, Dent disease or Fanconi syndrome. Nonetheless, genetic testing remains necessary for confirmation. Unlike other forms of hypophosphatemic rickets, phosphorus supplementation alone is the primary treatment, while active vitamin D metabolites should be avoided due to their potential to worsen hypercalciuria. Despite linear growth improvement seen with oral phosphate supplementation, isolated case reports additionally considered human recombinant growth hormone therapy with improved outcomes.