49-YEAR-OLD MALE WITH XLH*

  • 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)

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X-ray 1: Disease Progression
In Pelvis And Hips
49-year-old male X-ray of disease progression in pelvis and hips due to X-linked hypophosphatemia
44 years of age: Diffuse increased density of lilac wings and lumbosacral spine; bilateral enthesopathic calcifications extending from the superior acetabular walls.

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X-ray 2: Subtrochanteric
Pseudofracture
49-year-old male X-ray of subtrochanteric pseudofracture
44 years of age: Right subtrochanteric pseudofracture (arrow) incomplete along the medial cortical region.

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X-ray 3: Pseudofractures
In Femurs
49-year-old male X-ray of pseudofractures in femurs
44 years of age: Pseudofractures in the subtrochanteric right femur (arrow) and mid-left femoral diaphysis (arrow head); healing stress fracture present in left femoral neck medial cortex; enthesophytes and bilateral hip osteoporosis.
  • X-linked hypophosphatemia (XLH)
  • Treatment: calcitriol and phosphorus supplementation
  • 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
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.

49-year-old male case study timeline
  • 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/