ESPE Abstracts

Background: Hypophosphatemic rickets (HHR) is a vitamin D-resistant rickets and results in children in variable degrees of delayed walking, waddling gait, leg bowing, enlarged cartilages, bone pain, craniostenosis and growth failure. There are both inherited and acquired forms, where FGF23-dependent forms with X-linked dominant hypophosphatemic rickets (XLH) head of the list is the most prevalent genetic form; molecular defects of the sodium-phosphate co-transporter NPT2c unrelated to a FGF23 disturbance may cause hypophosphatemic rickets with hypercalciuria (HHRH).

Patients and Methods: We report four cases of HHR and retrospectively studied the clinical features, laboratory findings, genetic defects, as well as responses to treatment: one case with yet described FGF23-activating mutation and three cases with a new mutation in the SLC34A1 gene witch encodes the type II sodium-dependent phosphate co-transporter NPT2a.

Results: four patients from 2 families one case with yet described FGF23-activating mutation and Three related cases with new mutation of the SLC34A1 gene.

• In a girl who has been diagnosed at the age of 2 years and 10 months due to a gait disorder. The clinical-biological picture was compatible with hypophosphatemic rickets without hypercalciuria. The genetic study confirmed the diagnosis of dominant transmission hypophosphatemic rickets with mutation of the FGF23 gene. This mutation is described in the literature. The evolution under treatment was marked by a partial improvement of rickets. • Three children (two girls and one boy) who are from the same family. Hypophosphatemia was found in both children and parents, and in the latter especially in the father was also found the concept of urinary lithiasis. The diagnosis was made in the two sisters after the age of two years and their clinico-biological tables were compatible with hypophosphatemic rickets with hypercalciuria. At the brother's, the diagnosis was suspected at the age of two months in front of the family history and the discovery of a nephrocalcinosis. The genetic study carried out in one of the two girls as well as in the boy, confirmed the diagnosis of RHH with hypercalciuria, of recessive transmission, showing a homozygous mutation in the SLC34A1 gene. At the present state of our knowledge, this is the first mutation in the SLC34A1 gene causing HHRH, which is reported in the literature.

Conclusion: These results confirm the role of FGF23 in ADHR physiopathology and report for the first time HHRH caused by a homozygous SLC34A1 mutation, thereby further documenting the key role of the renal cotransporter NPT2a in the phosphocalcic metabolism.