Unresolved childhood symptoms of XLH may continue to manifest in adulthood

—Dr. Erik Imel, XLH adult specialist

HOME / DIAGNOSING XLH / CLINICAL PRESENTATION AND DISEASE PROGRESSION IN ADULTS

The lifelong presence of elevated FGF23 activity causes unresolved childhood symptoms to continue to progress into adulthood, paired with new, potentially irreversible symptoms that can appear due to ongoing active disease.1,2

Chronic hypophosphataemia is persistent among adults with XLH and may manifest as symptoms such as:

Persistent childhood symptoms

Bone biopsy showing osteomalacia

Osteomalacia2-4

Bowed legs is a symptom of XLH

Lower extremity abnormalities (leg bowing, knock-knees, windswept deformities)4

Short stature in XLH

Short stature2,4

Bone pain in XLH

Skeletal pain2,3,5

Abnormal head shape in a child with XLH

Craniosynotosis2,4

Protrusion in part of brain because of XLH

Chiari malformations2,4

New symptoms in adulthood

Mineralization of tendons and ligaments due to XLH

Enthesopathy (feet, knees, Achilles, hips, neck, spine)2,3,5

Narrowing of spine due to XLH

Spinal stenosis5

Osteoarthritis in the joints due to XLH

Osteoarthritis2,3,5

Fractures in the hips due to XLH

Fractures and pseudofractures2,3

Loss of hearing due to XLH

Hearing loss2,4

In addition to poor bone health, chronic hypophosphataemia continues to affect the muscles in the body. Adults may present with:

Muscle stiffness in adults due to XLH

Stiffness, pain, and weakness4

Wobbly walk due to muscle weakness from XLH

Waddling gait4

Chronic hypophosphataemia can also lead to dental defects by causing enlargement of the pulp chambers and erosion of the enamel.3 Symptoms manifest as:

Tooth infection in an adult with XLH

Dental abscesses3,4

Teeth and gum problems in an adult due to XLH

Periodontitis5

See the burden of XLH in the daily lives of children

References:

1. Carpenter TO, Imel EA, Holm IA, et al. A clinician’s guide to X-linked hypophosphataemia. J Bone Miner Res. 2011;26(7):1381-1388. 2. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphataemic rickets from infancy to adulthood. Endocr Connect. 2014;3(1):R13-30. 3. Ruppe MD, Zhang X, Imel EA, et al. Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphataemia. Bone Rep. 2016;5:158-162. 4. Ruppe MD. X-Linked Hypophosphataemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. 5. Skrinar A, Dvorak-Ewell M, Evins A, et al. The lifelong impact of X-linked hypophosphataemia: results from a burden of disease survey. J Endocr Soc. 2019;3(7):1321-1334. 6. Biosse Duplan M, Coyac BR, Bardet C, et al. Phosphate and vitamin D prevent periodontitis in X-linked hypophosphataemia. J Dent Res. 2017;96(4):388-395.