ESPN 54th Annual Meeting

ESPN 2022


 
ANTI-FGF23 TREATMENT IN A CASE OF AUTOSOMICAL RECESSIVE HYPOPHOSPHATEMIC RICKETS TYPE 2
NICOLA BERTAZZA PARTIGIANI 1 DAVIDE MENEGHESSO 1 GERMANA LONGO 1 ELISA BENETTI 1 MATTIA PAROLIN 1

1- PEDIATRIC NEPHROLOGY AND DIALYSIS UNIT, DEPARTMENT OF WOMEN’S AND CHILD’S HEALTH, UNIVERSITY OF PADOVA MEDICAL SCHOOL, 35128 PADOVA, ITALY
 
Introduction:

Hypophosphatemic rickets is a disorder of phosphate metabolism secondary,to alterations in FGF23 metabolism.Inactivating mutations of the ENPP1 gene(ARHR2)are responsible for the development of rickets, without necessarily developing an increase in FGF23,which is however inappropriate high for the phosphatemia.Burosumab,a recombinant anti-FGF23 monoclonal antibody, is  effective in the treatment of PHEX in pediatric patients,but its use in other forms of hypophosphatemic rickets is not proven.

Material and methods:

A 9-year-old girl,followed for ARHR2 due to homozygous ENPP1 mutation (c.1709A>Gp.Tyr570Cys),stopped supplementation therapy due to adverse events and subsequent difficult in compliance.For this reason,,treatment with Burosumab was started,initially at a dose of 0.4mg/kg every two weeks,and then increased to 0.8mg/kg 6 months after for partial response.Patient underwent regular clinical evaluation,laboratory exams, and radiological evaluation, to assess clinical improvement and to recognize signs of Generalized Arterial Calcification of Infancy(GACI), due to ENPP1 mutation. 

 

Results:

At the onset she presents valgus knee,mild nephrocalcinosis,marked hypophosphatemia(0.43mmol/L),increase in ALP(732 U/L),hyperphosphaturia and a slight increase in FGF23: 1.57pmol/L (0-0.8).The initial dose allowed a partial improvement,while increasing the dose to 0.8mg/kg,ALP reached 499U/L with serum phosphate of 0.75mmol/L,after 18 months.Growth was good(75-90th percentile).Wrist and knee radiographs demonstrate an improvement in the RSS score from 4 to 2.No signs of vascular calcification were detected.

Conclusions:

This case represents the first patient with ARHR2 effectively treated with Burosumab. Initially we scheduled a low dose considering the risk of vascular calcification in the ENPP1 mutation.However we increased the dose obtaining good results on phosphate and bone metabolism,demonstrating the efficacy and safety of Burosumab in this kind of mutation.