ESPE Abstracts

Background: X-linked hypophosphatemia (XLH) is a rare disease caused by PHEX pathogenic variants leading to elevated fibroblast growth factor 23 (FGF23). FGF23 was shown to modulate the immune system. Excessive FGF23 signalling in mice with chronic renal disease results in deficient recruitment of neutrophiles in the infected tissues and to inadequate immune reaction against bacterial aggression (Rossaint et al). An increased risk for recurrent infections due to immune deficiency has not yet been reported in XLH patients.

Case report: We present the case of a male patient aged 2 years and 9 months, with a novel hemizygous PHEX variant in exon 9 c.934-2A>T. The genetic and clinical diagnose was made at the age of 1 year and 8 months, followed by initiation of phosphate and active vitamin D supplementation. Medical history showed multiple infectious events: Covid at two months old, bronchiolitis at five and 12 months, multiple otitis media, bacterial pneumonia at 14 months, followed by chronic bronchitis. Burosumab was started at the age of two. At this point, he was still on cortisone inhalations and presented with residual cough and chronic otitis media, despite multiple antibiotic treatments. The child received all the vaccinations according to the French plan. Immunological investigations revealed an inadequate response to all vaccinations receivedbefore the age of two, showing no IgG production. Thoracic scan revealed an area of consolidation in the right lung. Microbiological analysis showed the presence of Haemophilus influenzae and Streptococcus pneumoniae. Lymphocyte T phenotype analysis was normal, no analysis of lymphocyte B function was performed at this moment. No abnormality of the white blood count was noticed. The virological analysis showed concomitant adenovirus, enterovirus and rhinovirus infections. Revaccination against diphtheria, Bordetella, tetanus, Haemophilus influenzae, poliomyelitis and hepatitis B was performed after 4 months of burosumab, and a combined antibiotic treatment (amoxicillin and cefuroxime) was started. Two months later, the post-vaccination immune analysis showed adequate antibody formation. An amelioration of the respiratory symptoms, as well as of the incidence of otitis media episodes was noticed already after 3 months of burosumab, during the follow-up visit.

Conclusion: We theorize that our patient presented an inadequate response to vaccination and suffered multiple infections due to a mechanism related to the elevated FGF23, with an amelioration of the immune status under FGF23 blocking treatment by burosumab, similarly to what was shown in an animal model (Rossaint et al).