What is XLH?

Whatever your journey to get you or your child diagnosed with XLH or a related disorder, you may be feeling relief, sadness or apprehension about the diagnosis.

Our understanding of this rare condition and suitable treatment is developing rapidly and there is a community of others that you can connect with through XLH UK. Whether it is research, support or advocacy, we’re here every step of the way to help.

The Basics

Hypophosphataemia means low levels of phosphate in the blood. Phosphate is a mineral that is essential for the normal formation of bones and teeth.

In most cases, the signs and symptoms of hereditary hypophosphataemia (hypo-phos-phat-emia) begin in early childhood. Because XLH is a genetic condition, it often affects several members of a family. The characteristics of the disease vary widely, even among affected members of the same family.

Skeletal abnormalities such as bowed or bent legs, below average height and irregular growth of the skull are early signs of XLH. Children may also present with delayed walking or waddling gait. Bone defects are common in children with untreated XLH, and when bone growth stops, bone deformities become irreversible and can be the source of continuing pain.

Adults with XLH can have symptoms such as osteomalacia (softening of the bones, which causes an increased risk of stress fractures and other complications), muscle weakness, pain and fatigue. Other manifestations of XLH include dental problems and hearing loss.

The aim of current treatment is to improve growth, reduce skeletal deformities and pain. For most people with XLH, clinical management consists of vitamin D supplementation and oral phosphate (often with dosing 4 to 6 times a day).

Burosumab is now recommended and available on the NHS for treating X-linked hypophosphataemia in children and young people who are still growing. This novel treatment addresses the underlying problem, rather than compensating for phosphate loss, so is effective in helping children to grow normally.

What Causes XLH?

X-linked dominant hypophosphataemia (XLH) is caused by mutations in the PHEX gene that inactivate the PHEX enzyme. This leads to errors in phosphate sensing and increased levels of fibroblast growth factor 23 (FGF23). Excess FGF23 causes impaired phosphate conservation and excessive phosphate excretion (also called phosphate wasting). It also suppresses vitamin D production, which causes reduced calcium and phosphate absorption.

X-linked means the gene is carried on the X chromosome and can be passed on to children of people carrying the gene, in a pattern which is explained here. Dominant means that you only need one faulty gene for XLH to be expressed, although XLH does not affect all individuals equally.

Whilst you may have inherited the gene, spontaneous cases (where this is the first person in the family to have the faulty gene) account for 20-30% of overall XLH cases.

Frequently Asked Questions

What is the prevalence of XLH?

Prevalence is defined by the Centre for Disease Control as the proportion of a population who is affected by a specific characteristic or condition in a given period. For rare conditions such as rare bone diseases, prevalence can be quite difficult to determine. This occurs because of difficulties in diagnosis and cases going undetected. The estimated prevalence of XLH is 3.9 per 100,000 births and a prevalence ranging from 1.7 per 100,000 children to 4.8 per 100,000 persons (children and adults) This would equate to approximately 350 adults with XLH in the UK in 2022.

Reference: https://doi.org/10.1007/s00198-021-05997-1

Should I tell my insurer about XLH?

Always inform insurers about any pre-existing medical condition or disability you have and about any medication you may be taking with you. Because XLH is rare, it may not be on the insurer’s list of risk-assessed conditions and you may be asked for conditions which ‘are similar’, to help them price the quote. Other patients with XLH have found that “osteomalacia” is accepted by several major insurers as an acceptable alternative description.

What are the main side effects of burosumab?

Some patients may develop reactions at the injection site, such as reddening of the skin, rash, swelling, or bruising. Speak to your prescribing doctor immediately if you have any reactions of any kind.

High levels of phosphorus in the blood have been reported in some patients taking burosumab, which may be related to a risk of high calcium levels in the kidneys. Your doctor will collect blood samples to monitor your levels and may adjust your dose.

What are the main side effects of phosphate and alfacalcidol treatment?

Abdominal distress – diarrhoea and nausea are the main side effects from taking oral phosphate supplements. It is essential to have your bloods monitored on a regular basis by an endocrinologist or rheumatologist. Excessive doses of phosphates may cause hypocalcaemia and hyperparathyroidism and could be dangerous.

Alfacalcidol is a type of vitamin D. You will need to have regular blood tests while you are taking the medicine so that your doctor can adjust your dose. Make sure you know the symptoms of too much calcium in your blood – these are losing your appetite, feeling thirsty, being sick (vomiting), feeling tired and losing weight. Speak to your doctor if you develop these symptoms.

It is important to remain hydrated while on phosphate and alfacalcidol treatment.

If you have another question, check out our Facebook group here. Alternatively you can email us at contact@xlhuk.org