Understanding rickets in osteopetrosis via a case: mechanisms and treatment implications

Osteopetrorickets is a rare autosomal recessive disease that affects many systems and is characterized by dense bone mass and paradoxical rickets due to insufficient resorption of calcified cartilage. Its rarity and presentation with nonspecific symptoms may cause delays in diagnosis. Early diagnosis and improvement of rickets accompanying bone marrow transplantation as a curative treatment option before the development of any irreversible complications are essential for prognosis. However, the etiopathogenesis and management of rickets treatment strategies are still controversial.

A 4-month-old female patient, whose loss of vision had been followed for 1.5 months, was admitted to our clinic with the request for a disability report. Clinical and laboratory findings were consistent with osteopetrorickets. Molecular analysis revealed a homozygous variant in the TCIRG1 gene. She was normocalcemic and hypophosphatemic, and the 25-OH vitamin D level was normal, while 1.25-dihydroxyvitamin D levels were quite high. Treatment was started with low-dose calcium replacement and calcitriol. The dose of calcitriol was gradually increased to 300 ng/kg/d, and a significant clinical response was achieved. Bone marrow transplantation was conducted at 8 months postnatally from an HLA-compatible non-related donor; nonetheless, the patient succumbed to respiratory problems on the 71st day following the procedure.

Nonspecific symptoms of osteopetrorickets should be considered for early diagnosis, as a timely intervention in the first months of life can be life-saving. The pathophysiology of rickets remains unclear, but low calcium-phosphorus product and resistance to 1.25-dihydroxyvitamin D appear to play key roles. High-dose calcitriol and cautious calcium supplementation may improve outcomes, though further research is needed to optimize treatment strategies.