37-year-old female with XLH*
- Age 2: diagnosed with X-linked hypophosphatemia (XLH) as a toddler
- Initiated oral phosphate and calcitriol and was compliant
- Age 13: XLH diagnosis was confirmed by genetic testing
- Mother and maternal grandmother had XLH
- Chiari malformation requiring two corrective surgeries
- Chronic ankle pain and swelling in joints
- Gait abnormalities
- Sustained pelvic fracture during childbirth
- Age 33: discontinued oral phosphate and calcitriol
XLH symptoms and associated complications in adulthood
- Age 35: presented to adult endocrinology with bowing of upper and lower extremities and joint stiffness in hips, knees, and ankles
- Physical exam
- Height, 5’2″
- Required the use of assistive walking device (cane) for long distances and handicap tags due to mobility challenges
- Tinnitus in right ear
- Calcifications noted on prior renal ultrasound
- Laboratory findings (see Table)
- Physical therapy evaluation
- Required assistance to rise from seated to standing position
- Tight hip flexors; limited range of motion in hips
- Prominent enthesophytes associated with the calcaneus bilaterally as well as ankle and midfoot arthritis; slight bowing seen bilaterally in lower legs (see X-ray 1)
- Hypertrophic bone formation occurring at the hip articulation and trochanters; sclerosis at the sacroiliac joints; slight bilateral bowing of femurs (see X-ray 2)
- Bowing deformity at each femur and degenerative changes of the knees including bilateral articular surface irregularities of the femoral condyles (see X-ray 3)
- Bilateral bowing of femurs, tibias, and fibulas; bones diffusely demineralized and bilateral narrowing of joint space compartment also noted (see X-ray 4)
Evaluation prior to CRYSVITA
- At 35 years old: prominent bilateral calcaneal enthesophytes; severe bilateral tibiotalar osteoarthritis; slight bilateral bowing in tibias and fibulas.
Diagnosis and initial treatment
- XLH diagnosis reconfirmed
- Treatment: CRYSVITA
- Age 36: initiated CRYSVITA and over time reported progressive improvement in joint stiffness
- After 10 weeks: CRYSVITA dose reduced after a 30-pound intentional weight loss due to diet and increased physical activity
- Reported adverse events
- Myalgias and fatigue, left knee swelling and pain during the first 3 months
- Adverse events managed with over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid pain medication; resolved with subsequent CRYSVITA injections
- No restless legs symptoms or injection site reactions were reported
- Laboratory findings: biochemical improvements after 35 weeks (see Table)
CRYSVITA treatment, 35 weeks
- At 35 years old: hypertrophic bone formation at hip articulation and trochanters (brackets); sclerosis at the sacroiliac joints; slight bilateral bowing of femurs.
- At 35 years old: degenerative changes of the knees including bilateral articular surface irregularities of the femoral condyles (arrows); diffusely demineralized bones with medial compartment joint space narrowing (arrow heads).
- At 35 years old: bilateral bowing of femurs, tibias, and fibulas; diffused demineralization of bones; bilateral narrowing of joint space compartment.
Laboratory test results
- 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; PTH, parathyroid hormone.
- aIndicates normal range, age, and sex matched. Note that normal range values may vary depending on reference dataset. The range in this table was provided by the treating physician.
- Patient was diagnosed with XLH as a toddler and suffered from XLH-associated symptoms throughout adulthood, including fractures, joint stiffness, pain, and diminished physical function
- At age 36, CRYSVITA was initiated and after nearly a year, patient demonstrated improvements in serum phosphorus levels and joint stiffness
- Adverse reactions reported during treatment included myalgia, fatigue, and left knee pain and swelling, which resolved within 3 months of treatment
- *The information for this case study was provided courtesy of Dr. Kathyryn 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. Not all patients will respond the same to CRYSVITA treatment. Results may vary. This case study does not claim to represent typical results.
Laboratory test results
|Test (reference rangea unit)||Results (age)|
|CRYSVITA 35 weeks
|Serum phosphorus (2.3-4.7 mg/dL)||1.6||2.6|
|1,25 (OH)2 (20-80 ng/mL)||40.3||-|
|25(OH)D (25-80 ng/mL)||35||60.6|
|BSAP (4.5-16.9 mcg/L)||25||19.1|
|PTH (16-88 pg/mL)||55||52|
|Creatinine (0.57-1.11 mg/dL)||0.74||0.70|