We report a case of hereditary hypophosphatemic rickets with hypercalciuria (Hereditary Hypophosphatemic Rickets with Hypercalciuria, HHRH) in a 13-year-old boy, referred for evaluation due to the onset of bilateral knee pain for about two years. Pain was intermittent and walking limiting and negatively affected quality of life. Negative family history of bone/joint pathologies and kidney stones. The parents are consanguineous (first cousins), have normal stature and no history of bone and mineral disorders. Physical examination revealed normal height and weight. There were no skeletal deformities. Hypophosphatemia was found on blood tests (2.7 mg/dl, normal for age 3.30-5.70) associated with high urinary excretion of phosphates (reduced TRP) and high urinary excretion of calcium (6.1 mg/ kg/day, normal <4 mg/kg /day). There were also elevated 1,25-vitamin D values (141 pg/ml, normal value 42-95 pg/mL) with inhibited parathyroid hormone (14 pg/ml, normal 15-65 pg/mL) and normal alkaline phosphatase values for the pubertal stage. The concentration of intact FGF23 was undetectable (<5 pg/ml, normal value 23.2- 95.4 pg/mL) in the patient’s serum. X-rays of the knees showed no obvious signs of rickets. The ultrasound of the urinary tract was normal, excluding the presence of nephrocalcinosis / nephrolithiasis. MRI of the distal femoral epiphyses disclosed abnormalities that were consistent with rickets. Genetic analysis PHEX gene was carried out negative. The FGF23-independent hypophosphatemia pattern directed the diagnostic suspicion towards a form of tubulopathy. Possible diagnostic hypotheses were, HHRH, Dent disease, Fanconi syndrome, or idiopathic familial hypercalciuria. Genetic analysis showed a homozygous mutation of the variant c.448 + 1G> A in the SLC34A3 gene, pathogenetic for hereditary hypophosphatemic rickets with hypercalciuria. The accurate diagnosis of HHRH has important therapeutic implications. In our patient, phosphate therapy caused complete remission of symptoms after about 2 months from the start of therapy with normalization of the urinary calcium. In patients with HHRH, unlike other forms of rickets, the addition of active vitamin D can create complications, such as hypercalcemia, nephrocalcinosis, and renal damage.
15 Sep 2022 - 17 Sep 2022