Chronic hypophosphatemia leading to the diagnosis of autosomal recessive hypophosphatemic rickets type 2 caused by a novel pathogenic variant in ENPP1.
Peihsuan Tsai, Naim M Maalouf
✦ AI-curated · Sources linked
Case in brief
Two brothers in their late 40s presented with chronic hypophosphatemia and elevated serum parathyroid hormone (PTH) levels. They exhibited extra-skeletal calcifications and significant bone microarchitecture abnormalities. One brother had long-standing hypophosphatemia with multiple complications, while the other underwent parathyroidectomy for suspected primary hyperparathyroidism, leading to postoperative hypoparathyroidism. Genetic testing revealed a novel pathogenic variant in ENPP1, confirming autosomal recessive hypophosphatemic rickets type 2.
What made this case unusual
The case highlights the diagnostic challenges of adult-onset autosomal recessive hypophosphatemic rickets type 2, particularly the misdiagnosis of primary hyperparathyroidism due to overlapping clinical features.
Diagnostic / clinical pearl
Clinicians should consider autosomal recessive hypophosphatemic rickets type 2 in adults with chronic hypophosphatemia and elevated PTH, especially when accompanied by extra-skeletal calcifications.
Why it matters
Accurate genetic diagnosis is crucial as ARHR2 can mimic other metabolic bone disorders, emphasizing the importance of recognizing FGF23-mediated phosphate wasting for appropriate management.