X-linked hypophosphataemia (XLH) is the most common form of inherited hypophosphataemic rickets, caused by loss-of-function mutations in the gene encoding phosphate-regulating endopeptidase homologue X-linked (PHEX), resulting in excess circulating fibroblast growth factor 23 (FGF-23).1,2 In children, therapy includes daily oral phosphate and active vitamin D analogue (alfacalcidol or calcitriol) supplementation, but is associated with gastrointestinal side effects and hyperparathyroidism.2 In adults who have undergone conventional therapy during childhood, but are still symptomatic, conventional treatment is usually maintained or re-initiated in order to reduce pain as a result of micro-fractures and/or osteomalacia; however, the side effects of conventional treatments persist.2 Here we report the case of an adult patient with XLH and the impact of the side effects of conventional therapy since his diagnosis.
The patient was diagnosed with XLH at aged 4 years and had a history of leg bowing, which had previously resolved with treatment. At age 20, he presented with pain during walking. He had no hearing or dental issues or limb deformities and was being treated with oral phosphate supplementation (3050 mg/kg t.i.d.) and alfacalcidol (1.53.0 µg q.d.). Whilst on conventional treatment, growth, leg deformities, dental health and serum levels of alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium, and creatinine were monitored every 6 months, as were urine levels of calcium and creatinine. A renal ultrasound was performed every 12 months. The patient developed medullary nephrocalcinosis in his right kidney at age 9 and a large parathyroid adenoma at age 20 and was referred to a surgeon. Both findings were thought to be related to long-term conventional therapy with oral phosphate and alfacalcidol, so therapy was discontinued. Following treatment discontinuation, most recent serum levels were as follows: high ALP, 1622.6 U/L; high PTH, 1403.0 ng/L; low phosphate, 0.93 mmol/L and urine calcium/ creatinine ratio was 0.07.
In this adult case of XLH, long-term treatment with oral phosphate and vitamin D supplementation therapy since childhood has resulted in significant side effects. Therapies targeting the underlying pathophysiology of the disease, i.e. FGF23 excess, and with fewer side effects are desirable.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology