IMPE Abstracts

Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare cause of genetic rickets with autosomal recessive inheritance. It is caused by a defect in the type IIc sodium dependent phosphate cotransporter (SLC34A3 gene), one of the main responsible of phosphate homeostasis in the kidney. The clinical, biochemical and radiological characteristics are variable among affected individuals.

Clinical case: We report a 12-year-old girl referred by pediatric traumatologist with diagnosis of genu valgum in order to assess bone mineral metabolism. She evolved with lower limb (LL) weakness and difficulties to perform activities of daily living such as climbing stairs. Relevant family history does not emerge during the directed questioning. Physical examination: weight 41,7 kg (-0,14 SD), height 135,6 cm (-1,56 SD), pubertal (Tanner stage IV), genu valgum is confirmed (intermalleolar distance: 16,2 cm). Biochemical studies showed hypophosphatemia, normal calcium, hypercalciuria, elevated alkaline phosphatase, slightly decreased vitamin D, low PTH, variable tubular phosphate reabsorption, slightly increased FGF-23 and very high 1,25-dihydroxy vitamin D levels. Radiological assessment (both hands and entire LL): metaphyseal irregularity predominantly in the ulna, increased cortical thickness and misaligned axes of the LL. Bone densitometry: lumbar spine L1-L4: 0,751 g/cm2 (Z-score: -1,6 SD) and total body: 0,542 g/cm2 (Z-score:-3,0 SD). Renal ultrasound revealed bilateral medullary nephrocalcinosis. Collectively, the clinical, biochemical, and radiological findings were consistent with HHRH. The genetic study showed a variant in the SLC34A3 gene that promotes the substitution of the amino acid glycine at codon 166 for aspartate (p.Gly166Asp). It has not been previously reported and, although it is classified according to the American College of Medical Genetics and Genomics as a variant of uncertain significance (VUS), it is located in a fairly conserved region of the protein, which would suggest a potential deleterious effect. The patient underwent surgical correction of her genu valgum and treatment with oral phosphate was indicated.

Conclusion: This case highlights the relevance of bone mineral metabolism assessment in children with bone deformities and the importance of including serum phosphate levels in the initial studies. Some congenital disorders may present late in adolescence or early adulthood, so genetic origin cannot be ruled out when presentation is late. On the other hand, it is essential to differentiate HHRH from other causes of hypophosphatemic rickets since, although they share clinical and biochemical characteristics, the treatment differs for each one.