DIAGNOSE XLH

Misdiagnosis can lead to inappropriate disease management, which can lead to worsening of symptoms of XLH. XLH can be misdiagnosed as nutritional rickets, osteomalacia, hypophosphatasia, Pyle’s disease, and physiologic bowing.1

A diagnosis of XLH is typically based on clinical and biochemical findings in combination with genetic findings.2


XLH is a hereditary disorder. A detailed family history may help identify undiagnosed individuals.

 

Genetic inheritance of X-linked hypophosphatemia (XLH)

WITH KNOWN FAMILY HISTORY OF XLH

XLH is inherited in an X-linked dominant pattern.2 In a family with a history of XLH, screen for other family members. This can help you identify previously undiagnosed individuals.

WITHOUT A KNOWN FAMILY HISTORY OF XLH

About 20% to 30% of XLH cases are spontaneous.3 Ask about his/her medical history of short stature, rickets, osteomalacia, osteoarthritis, and dental abscesses, which may indicate XLH.

GENETIC TESTING IS IMPORTANT TO CONFIRM A DIAGNOSIS OF XLH.

Learn more about a program offering no-charge genetic testing to eligible
patients suspected of having hypophosphatemia.

The following are predominant clinical findings in children and adults.

Children

Signs of XLH in children: bowed legs, rickets, knock-knees

Rickets, lower extremity bowing, leg abnormalities, pain, short stature, and gait disturbances.1,2,4 Confirm skeletal findings through radiography.1 Other signs and symptoms may also include dental abscesses, craniosynostosis, and Chiari malformations.2,4

Adults

Signs of XLH in adults: osteomalacia, enthesopathy, pseudofracture

Adults with XLH may present with osteomalacia manifesting as bone and muscle pain, enthesopathy, fractures, and pseudofractures. Other signs and symptoms may also include waddling gait, dental abscesses, and hearing loss.1,2,4,5

SYMPTOMS OF XLH WILL CONTINUE TO PROGRESS IF UNTREATED.

It is critical to begin management of XLH early to prevent further damage caused by underlying osteomalacia.

Include age- and gender-normalized levels of serum phosphorus in metabolic panels for an accurate diagnosis. Low phosphate levels and a low TmP/GFR ratio are the most relevant biochemical findings for XLH.1,2

Key biochemical findings for xlh

Biochemical serum test for X-linked hypophosphatemia

Other biochemical findings that may be useful for establishing the diagnosis of XLH include serum alkaline phosphatase (ALP) levels and FGF23 levels.

Alkaline phosphatase can be a good marker of skeletal health in children but not necessarily for adults.2

1,25(OH)2D = 1,25-dihydroxyvitamin D (calcitriol); 25(OH)D = 25-hydroxyvitamin D (calcifediol); ALP = alkaline phosphatase; PTH = parathyroid hormone; TmP/GFR = ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate; XLH = X-linked hypophosphatemia.

ELEVATED FGF23 IS THE UNDERLYING CAUSE OF XLH.

Testing serum FGF23 may help to confirm a diagnosis of XLH. Learn more about FGF23 testing.

DR. CARPENTER'S EXPERIENCE WITH DIAGNOSING XLH

Signs and symptoms of XLH

Watch Dr. Carpenter discuss the lifelong and progressive symptoms of XLH.

Biochemical findings

Watch Dr. Carpenter discuss the common biochemical findings in patients with XLH.

Family history

Watch Dr. Carpenter discuss the dominant inheritance pattern of XLH.

Burden of disease

Watch Dr. Carpenter discuss the lifelong burden of XLH for pediatric patients.

References:

1. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381-1388. 2. Ruppe MD. X-linked hypophosphatemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews®. University of Washington, Seattle; 1993-2022. Published February 9, 2012. Updated April 13, 2017. https://www.ncbi.nlm.nih.gov/books/NBK83985/ 3. Gaucher C, Walrant-Debray O, Nguyen TM, Esterle L, Garabedian M, Jehan F. PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets. Hum Genet. 2009;125(4):401-411. 4. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect. 2014;3(1):R13-30. 5. X-linked hypophosphatemia. Genetic and Rare Diseases Information Center (GARD). Updated February 26, 2018. Accessed March 14, 2022. https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphatemia 6. Santos F, Fuente R, Mejia N, Mantecon L, Gil-Peña H, Ordoñez FA. Hypophosphatemia and growth. Pediatr Nephrol. 2013;28(4):595-603.