Development of the Legs: In children the first thing that is noticed is that there is some bowing of the legs. It can be missed initially as toddlers often have a degree of mild ‘physiological’ bowing. Children with XLH may walk late or have pain in their legs, with swelling of the ankles, knees and wrists or a waddling gait. These are all signs of rickets and children may be misdiagnosed as having vitamin-D deficiency rickets.

Normally the diagnosis of rickets is made by radiographs. Once rickets is diagnosed and vitamin D deficiency is ruled out, then the diagnosis of hypophosphataemic rickets is confirmed using paired urine and blood tests. This looks at how much phosphate is being lost in the urine, combined with low blood phosphate level (phosphate wasting). Other clues to the diagnosis may be tooth abscesses or affected family members.

The key to making the diagnosis is the doctor thinking about this as a possibility. Sometimes the phosphate can be in the lower part of the normal range and children can go for many months and years before someone looks more closely. After establishing the clinical diagnosis, the genetic diagnosis can be made. Most of the time it is due to a mutation in PHEX but there are other causes of hypophosphataemia.

Development of the Skull: Some children with XLH may have craniosynostosis, a condition where the skull bones fuse prematurely, leading to abnormal head shape and potential developmental issues. Surgery is the primary treatment method and aims to release the fused sutures and allow for normal brain growth. The long-term prognosis varies depending on individual factors, but early diagnosis and intervention are crucial for better outcomes.

Chiari type 1 malformation is a structural problem in the brain where the cerebellar tonsils extend below the opening at the base of the skull. It is detected in 25–50% of children with XLH, by use of cranial MRI or CT scan. Most cases are asymptomatic, but compression of the lower brainstem and upper cervical cord might cause symptoms requiring surgical correction.

In adults with XLH, symptoms can vary in severity over time, and some individuals may have milder or more severe manifestations of XLH.

One of the most prevalent symptoms is bone pain, which can be chronic and affect different parts of the body. Adults with XLH may experience pain in their legs, arms, and lower back, making it challenging to perform regular activities.

Because of phosphate wasting, adults with XLH are also at a higher risk of developing bone deformities, such as bowed legs or an abnormal curvature of the spine (kyphosis). Stress fractures may not heal as easily and bones are at risk of insufficiency fractures because they are softer (osteomalacia).  Joints may be stiff and develop enthesopathies (abnormalities where tendons and ligaments attach to bones). These deformities can lead to further discomfort and difficulty in movement.

Adults with XLH may also suffer from muscle weakness, which can contribute to reduced physical strength and endurance. This weakness may affect their ability to walk long distances or participate in physical activities.

In addition to bone and muscle-related symptoms, XLH can cause dental issues and hearing problems.