Case Study Stresses Importance of Early Diagnosis, Awareness

The case of a woman diagnosed with X-linked hypophosphatemia (XLH) relatively late in life — after the condition had already taken a substantial toll on her physical health and quality of life — highlights the importance of early diagnosis and physician awareness about the disorder, researchers say.

The case study, “X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan,” was published in the Annals of Medicine and Surgery.

XLH is one of nearly 400 types of skeletal disorders characterized by abnormalities of cartilage and bone growth. Advances in diagnostic methods and treatments have been made in recent years. However, getting a correct diagnosis can still be challenging, in large part because some physicians may not have the knowledge required to identify these rare conditions. XLH is estimated to affect one in 20,000 individuals.

The case report describes a 43-year-old, wheelchair-bound woman who was seen at the metabolic bone clinic of Aga Khan University Hospital in Pakistan. The patient was about four feet tall and had no teeth, but had extreme bowing deformities in her legs, arms, and back.

She had first experienced a low-trauma fracture (a broken bone where little force was needed for the break, such as falling from a short height) at age 8. Subsequently, she experienced multiple additional low-trauma fractures. On several occasions, surgery was performed to help heal these fractures (via the placement of rods).

The patient’s disability progressed over time, and she became wheelchair-bound. After completing middle school, she was unable to pursue further education because of her illness.

When examined at the hospital, she was using dental prosthetics as a result of having lost all her teeth. She underwent a complete metabolic workup. Laboratory tests revealed abnormally low phosphorus levels in the blood, as well as abnormally high levels of parathyroid hormone, which is involved in regulating calcium and phosphate levels.

This led to a preliminary diagnosis of hypophosphatemic osteomalacia — or bone abnormalities due to low phosphate levels. Then, the patient underwent genetic testing of several genes associated with this condition. The testing revealed a mutation in the gene PHEX, confirming a diagnosis of XLH.

The patient was given supplemental potassium and alfacalcidiol (a form of vitamin D), and her pain eased after about four weeks. She was also offered education about XLH and provided with instructions to avoid falls.

“Diagnostic delay in this patient resulted in increased disabilities affecting her mobility and [lifestyle],” the researchers wrote.

This is the second documented case of XLH in Pakistan, after the first case was reported in 2004; however, that case was based on family history and lab investigations, the researchers wrote. The frequency of XLH in Pakistan is likely underreported, the team added.

Early diagnosis and treatment have been associated with better clinical outcomes and improved life quality for bone disorders worldwide. As such, the researchers stressed the need for education and awareness about these disorders, especially in countries like Pakistan where healthcare resources may be more limited.

“There is a need to educate and assist physicians about the rare bone diseases in Pakistan for improving the provision of care,” the investigators wrote.

Increased access to genetic counseling is another important need, as is the implementation of specialty centers, they added.