SEE THE SYMPTOMS AND DIAGNOSIS JOURNEYS OF REAL PATIENTS WITH XLH
49-YEAR-OLD MALE WITH XLH*
- Medical history
- Diagnosis and initial treatment
- Disease progression
- Laboratory test results
- Case summary
Medical history
- During childhood
- 6 years of age: humerus fracture from jumping off a moving truck
- Poor dentition of both primary and secondary teeth with multiple cavities and abscesses
- 11 years of age: reported “bone disease” due to chronic bone and joint pain
- Pediatrician diagnosed post-streptococcal arthritis
- Mild leg bowing; reported short stature compared to peers
- Early to mid-twenties
- Lost most teeth by early twenties
- Acute worsening of bone and joint pain
- Suspected inflammatory arthritis; treated with anti-inflammatory medication
- 44 years of age
- Presented with acute exacerbation of chronic weakness and right hip pain
- Required the use of prescription pain medication, including hydrocodone acetaminophen
- Reported no previous diagnosis of rickets or any medical management of low phosphorus
- Family history
- Short stature and bowing of the lower legs in mother (height, 4’11”), three brothers, and two nieces; all had multiple fractures
- Physical exam
- Height, 5’3”; weight, 230 lbs
- Ambulating with assistance of a walker; knees in varus alignment
- Pain with internal rotation of hips (left worse than right); 4/5 motor strength in both proximal and distal muscle groups
- Poor dentition and missing most secondary teeth
- X-rays
- Pelvis and hips: diffuse increased density of the bones, particularly in the iliac wings and lumbosacral spine; enthesopathic calcifications extending from the superior acetabular walls bilaterally (See X-ray 1); right subtrochanteric pseudofracture identified, which was incomplete along the medial cortical region (See X-ray 2)
- Femurs: pseudofractures in the subtrochanteric right femur and mid-left femoral diaphysis; healing stress fracture present in the medial cortex of the left femoral neck; enthesophytes and bilateral hip osteoporosis also noted (See X-ray 3)
- Laboratory findings (See Table)
- Presented with acute exacerbation of chronic weakness and right hip pain
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X-ray 1: Disease Progression
In Pelvis And Hips

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X-ray 2: Subtrochanteric
Pseudofracture

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X-ray 3: Pseudofractures
In Femurs

Diagnosis and initial treatment
- X-linked hypophosphatemia (XLH)
- Treatment: calcitriol and phosphorus supplementation
Disease progression
- 44 years of age: after XLH diagnosis, under went left hip replacement surgery
- Developed worsening right hip pain; underwent right hip replacement surgery 3 months later
- 46 years of age: developed worsening left shoulder and knee pain requiring multiple orthopedic visits for steroid injections
- Developed loosening of hardware in left hip due to osteomalacia and continued to require frequent steroid therapy
- Reported being compliant to conventional therapy
- 47 years of age: under went knee replacement therapy evaluation
- Unable to work and required disability benefits
- Dependent on assistive walking devices
- Developed ringing in ears and hearing loss
- Referred to pain management; nerve pain medication added to regimen with little pain improvement
- Laboratory findings (See Table)
- 49 years of age: underwent left knee replacement; advised a right total knee replacement was needed as well
- Insurance started denying coverage for calcitriol and phosphorus therapy on the basis that these medications are supplements/vitamins
- Medication was continued with coverage through a grant
- Patient reported compliance with conventional therapy; developed worsening back, neck, and hand pain
- Could not afford dentures and had difficulty maintaining adequate nutrition
- 3 months later: alternate therapeutic options were explored
Laboratory test results
Test (reference rangea unit) | Results 44 – years | Results 47 – years |
---|---|---|
Serum phosphorus (2.4-5.7 mg/dL) | 2.1 | 2.1 |
1,25 (OH)2 (20-80 ng/mL) | 31 | 25 |
25(OH)D (25-80 ng/mL) | 33 | 37 |
BSAP (6.5-20.1 mcg/L) | 39.2 | 32.0 |
PTH (16-77 pg/mL) | 95 | 48 |
Creatinine (0.72-1.25 mg/dL) | 0.83 | 1.12 |
FGF23 (<180 RU/mL) | 73 | 383 |
1,25 (OH)2, 1,25 dihydroxy vitamin D; 25(OH)D, 25-hydroxy vitamin D (calcifediol); BSAP, bone-specific alkaline phosphatase, also known as BAP; FGF23, fibroblast growth factor 23; PTH, parathyroid hormone.
aIndicates normal range, age, and sex matched. Note that normal range values may vary depending on reference dataset. These ranges were provided by the treating physician.
Case summary

- The patient was not accurately diagnosed with XLH until age 44
- There is a spectrum of disease for XLH,1 and the patient’s symptoms were not previously attributed to XLH
- Symptoms of XLH progressed throughout adulthood and had long-term impact. The patient:
- Required surgeries and developed worsening pain
- Required the use of assistive walking devices
- Developed hearing loss
- Needed dentures
- Alternative therapeutic options were explored
*The information for this case study was provided courtesy of Dr. Kathryn McCrystal Dahir, Professor of Medicine, Department of Endocrinology, Vanderbilt University Medical Center, Nashville. This case study represents a real patient and is intended to be illustrative, not a recommendation for treatment or management. Results may vary. This case study does not claim to represent typical results.
Reference:
1. 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 March 14, 2022. https://www.ncbi.nlm.nih.gov/books/NBK83985/