Bone Abstracts

Background: Primary de Toni-Debré-Fanconi syndrome is a metabolic disorder characterized by hypophosphatemic rickets or osteomalacia, renal tubular acidosis, renal glycosuria, generalized aminoaciduria. It is a non-FGF23-mediated hypophosphatemic disorder, with primary defect in proximal tubular dysfunction. The orthopaedic sequela of this rare disorder in the literature is scarce.

Presenting problem: We present a clinical case of a 10-year-old female with primary de Toni-Debré-Fanconi syndrome resulting in hypophosphatemic rickets treated with phosphorus, calcitriol and sodium citrate with a satisfactory orthopaedic outcome.

Clinical management: The patient presented with genu varum with biochemical and radiographic rickets at age 1 year. She was initially diagnosed with vitamin D deficiency rickets and treated with ergocalciferol at various doses for 2 years with no improvement. She had complaints of polyuria, polydipsia, enuresis, and bone pain. Further investigations showed phosphaturia, glycosuria, proteinuria, and acidosis. Diagnosis of hypophosphatemic rickets due to primary de Toni-Debré-Fanconi syndrome was subsequently made, without evidence of cystinosis. Respiratory chain enzyme analysis identified a complex I mitochondrial deficiency as underlying cause. She was then started on low dose phosphate therapy, and sodium citrate at age 3 years with some improvement in bone pain but continued bone deformity. At her first evaluation at the Pediatric Metabolic Bone Clinic at age 5 years, she was noted to have swelling of her knees with genu valgus deformities of 24 degrees. Her phosphate dose was increased to 70 mg/kg per day and she was started on calcitriol 0.5 μg/day. She had significant improvement in her genu valgum with normal growth. By age 10 years, her genu valgus deformities were 4 degrees with healing of rickets. She had no fractures. Her bone mineral density (BMD) at age 10 years showed normal lumbar BMD Z-score at 0, while total body BMD Z-score was low at −2.2.

Discussion: This patient had excellent improvement in bone deformity associated with hypophosphatemic rickets, despite late proper medical intervention. Non-FGF23-mediated hypophosphatemic rickets may have better response to medical therapy as compared to FGF23-mediated hypophosphatemic rickets in which bone deformity continues to progress on medical therapy and surgical correction is often required.