Ankle Pain in XLH Adults May Indicate Inflammation, Case Study Says

X-linked hypophosphatemia (XLH) can cause inflammation of ligaments, tendons, or joint capsules where they attach to bone — a condition called enthesopathy — and result in ankle pain, a case study suggests.

The study, “Alternative causes of ankle pain in a patient with enthesopathy and X-linked hypophosphataemia,” was published in the journal The Lancet.

XLH is caused by mutations in the PHEX gene, which lead to defective absorption of phosphate by the kidneys. Insufficient phosphate leads to growth stagnation, as well as rickets and osteomalacia — the abnormal softening of bones, making them more prone to fractures.

In adults with XLH, poor mineralization of bones is the cause of common complaints of joint pain in the knee, hip, and back.

Treatment with phosphate supplements and calcitriol (the active form of vitamin D) improves bone formation and growth rate in children, but fails to help adult patients with joint pain and with enthesopathy.

In the report, clinicians at the Princess Alexandra Hospital, in Brisbane, Australia, described the case of a 43-year-old Australian man referred to the hospital due to increasing pain in both ankles. Three days before the pain started, he was admitted to the hospital due to a bacterial skin infection on the upper arm.

The patient was diagnosed with XLH as a child and was treated until early adulthood with calcitrol and phosphate supplements. He had a family history of XLH and had a Chiari malformation, in which the lower part of the brain pushes down into the spinal canal.

When he was 35, the patient became infected with hepatits C, which was successfully treated with interferon therapy.

Clinical examination revealed he had moderate pain in joint movements and pronounced bone deformities in his feet. In the midfoot region, he had pes planus, or flatfoot, and hypertrophic (enlarged) growth. In addition, the sole of the foot was tender, but the patient had no monosodium urate crystals deposits, a symptom of gout.

X-rays showed significant bone formation in the entheses — tissue between tendons or ligaments and bone — in the hind and midfoot. Fluid analysis of the ankle joint showed signs of gout.

“We therefore attributed his symptoms to a gout flare precipitated by acute kidney injury and septicaemia,” the investigators wrote.

After he was treated with colchicine (sold as Colcrys, among other names), a CT scan showed that his gout was resolved. Yet, his ankle joint pain persisted.

The clinicians then investigated other causes for the ankle pain, including XLH.

Blood analysis showed low phosphate levels — 0.63 mmol/L (normal range 0.75–1.5) — and low calcitriol, at 19 picomol/L (normal range 48–190).

Further examination revealed he had extensive enthesopathy affecting the ankles, feet, and pelvis.

Overall, the findings support that enthesopathy can occur in several underlying diseases, including heritable forms of low phosphate levels, the researchers said.