ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This case-series describes the clinical characteristics and genetics of 8 patients with hereditary hypophosphatemic rickets (HHR). It highlights the challenges faced in diagnosis and management.

Hypophosphatemic rickets (HHR) is often underdiagnosed or misdiagnosed, leading to delays in proper treatment. Misdiagnosis can result in inappropriate therapies and worsening of the condition. The cases presented highlight the importance of comprehensive genetic testing for accurate diagnosis, as traditional diagnostic methods may not detect all variants.

HHR is caused by mutations in several genes, with PHEX being the most common. However, the expressivity of these mutations can vary, even within the same family, complicating diagnosis and management. Conventional treatments, primarily phosphate supplements and active vitamin D analogs, are often insufficient in managing HHR. Poor compliance due to side effects and the burden of frequent dosing is common. Burosumab, a new treatment option that targets FGF23, has shown promise in improving outcomes, but access to this therapy is not equitable, with many patients unable to afford it.

The authors present 8 clinical vignettes of patients with HHR encountered in a tertiary pediatric endocrinology centre in the United Arab Emirates. It describes clinical features, genetics, and management of 4 cases of X-linked hypophosphatemia ( PHEX mutations), one each of autosomal recessive HHR ( DMP1 mutation) and autosomal recessive vitamin D-dependent rickets type 1A ( CYP27B1 mutation), and two cases of distal renal tubular acidosis with FOXI1 mutation-associated HHR. These cases emphasize the need for individualized treatment plans and the potential benefits of newer therapies like Burosumab.

These cases underscore the complexities of managing HHR and advocates for improved diagnostic and treatment protocols to ensure better patient care. There is a call for better awareness, earlier genetic testing, and more consistent access to effective treatments like burosumab. Equitable access to such therapies is crucial to improving patient outcomes.

References: 1. Gonzalez-Lamuno, D., 2020. Hypophosphataemic rickets: diagnosis algorithm-how not to make a mistake. Adv. Ther. 37 (Suppl. 2), 95-10495–104. 10.1007/s12325-019-01184-1.2. Haffner, D., Emma, F., Eastwood, D.M., Duplan, M.B., Bacchetta, J., Schnabel, D., et al., 2019. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat. Rev. Nephrol. 15 (7), 435–455. 10.1038/s41581-019-0152-5.