Adult Presentation of X-Linked Hypophosphatemia
Abstract
:1. Introduction
2. Diagnosis of Adult XLH
3. Symptoms of Adult XLH
3.1. Pseudofracture and Fracture
3.2. Muscle Weakness
3.3. Dental Health
3.4. Enthesopathy
3.5. Osteoarthritis
3.6. SHPT/THPT
3.7. CKD
3.8. Hypertension and Left Ventricular Hypertrophy
3.9. Hearing Loss
4. QOL of Adult XLH
5. Transition of XLH Patients
6. Treatment of Adult XLH
6.1. Indication and Selection of Treatment
6.2. Conventional Therapy (Active Vitamin D and Phosphate Supplementation)
6.3. Burosumab
7. Remaining Problems and Future Research Topics in Adult XLH Patients
8. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Observation | Conventional Therapy | Burosumab |
---|---|---|
BAP (≤upper limit of the reference range) | BAP (>upper limit of reference range) with eGFR ≥ 45 mL/min/1.73 m2 | BAP (>upper limit of the reference range) with conventional treatment |
Stature (≥−1.0 SD) | Short stature (−2.0 ≤ −1.0 SD) with eGFR ≥ 45 mL/min/1.73 m2 | Short stature (<−2.0 SD) |
Mechanical axis of the leg within zone 1 [43] | Deviation of the mechanical axis of the leg into zone 2 [43] with eGFR ≥ 45 L/min/1.73 m2 | Deviation of the mechanical axis of the leg into zone 3 or greater [43] or history of corrective surgery for leg deformity |
No history of pseudofracture/bone pain/fracture in weight-bearing bone or odontitis/tooth abscesses | Pseudofracture/bone pain in weight-bearing bone or odontitis/tooth abscess once with eGFR ≥ 45 mL/min/1.73 m2 | Pseudofracture/bone pain in weight-bearing bone or odontitis/tooth abscesses more than two times or more than once with conventional treatment or once requiring impending surgery |
No response or trivial response to burosumab | Fracture in weight-bearing bone | |
Severe adverse event with burosumab | Uncontrolled severe SHPT with conventional treatment (e.g., peak intact PTH ≥ twice the upper limit of the reference range); | |
THPT; | ||
Patients with symptoms described in the “conventional therapy” and eGFR < 45 mL/min/1.73 m2; | ||
Severe adverse event with conventional therapy |
Priority | Event | Action |
---|---|---|
Initiation of treatment | Start with active vitamin D (0.50 μg b.i.d. for calcitriol or 1.0 μg s.i.d. for alfacalcidol) After 1 to 2 weeks, start phosphate supplementation (800 mg q.i.d.) | |
Range of dosage | Calcitriol: 0.50 to 0.75 μg b.i.d., alfacalcidol: 0.75 to 1.5 μg s.i.d. Phosphate supplementation: 750 to 1600 mg q.i.d. | |
Initial phase | Adjust phosphate supplementation for a period of time by 100 mg Goal: peak phosphate 1 within lower 50% of the reference range; laboratory test: every one to four weeks | |
Maintenance phase (after 12 to 18 months) | Adjust phosphate supplementation for a period of time by 100 mg Goal: BAP within the reference range Laboratory test: every 3 months Uncontrolled BAP: change the treatment to burosumab | |
High | Severe SHPT (peak intact PTH ≥ 2 × upper limit of the reference range) | Immediately decrease phosphate supplementation by 100 mg or more Increase active vitamin D (0.25 μg daily for calcitriol and 0.25 to 0.5 μg daily for alfacalcidol) After 1 to 2 weeks, increase phosphate supplementation Uncontrolled severe SHPT: change the treatment to burosumab |
High | Development of THPT (hyperparathyroidism with the value of calcium ≥ the middle of the reference range) | Immediately quit conventional therapy Initiate allosteric modulation of calcium sensing receptor Try to prevent dehydration Conduct parathyroidectomy for all recognizable glands, otherwise continue allosteric modulation of the calcium sensing receptor in patients with contraindication for surgery Change the treatment to burosumab afterward |
High | Overadjustment of peak phosphate within upper 25% of the reference range or over | Immediately decrease phosphate supplementation by 100 mg or more |
High | Progression of CKD to eGFR < 45 mL/min/1.73 m2 | Decrease conventional therapy Change the treatment to burosumab in patients who still need phosphate supplementation (uncontrolled BAP with active vitamin D). |
Priority | Event | Action |
---|---|---|
Initiation of treatment | 1.0 mg/kg body weight (up to 90 mg) subcutaneous injection every four weeks Response to burosumab should be confirmed by peak phosphate 1; Concomitant use of active vitamin D and phosphate supplementation is not recommended or is prohibited unless another medical condition requires it | |
Trough phosphate 2 within the higher half of the reference range | Decrease burosumab dose by 0.2 to 0.3 mg/kg Subsequently, fine tune burosumab dose by 0.1 mg/kg to target trough phosphate within lower half of the reference range | |
High | Trough phosphate over the reference range | Suspend burosumab until phosphate values fall below the normal range Restarted burosumab at approximately half the initial starting dose |
No or trivial response at peak phosphate | Rule out vitamin D deficiency by measuring 25OHD Severe SHPT: continue burosumab 3 to 6 times and confirm improvement in peak phosphate Continuing no response or trivial response after problems above are ruled out or addressed; change treatment to conventional therapy | |
High | THPT | Initiate allosteric modulation of the calcium sensing receptor Try to prevent dehydration Conduct parathyroidectomy for all recognizable glands, otherwise continue allosteric modulation of the calcium sensing receptor in patients with contraindication for surgery |
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Ito, N. Adult Presentation of X-Linked Hypophosphatemia. Endocrines 2022, 3, 375-390. https://doi.org/10.3390/endocrines3030030
Ito N. Adult Presentation of X-Linked Hypophosphatemia. Endocrines. 2022; 3(3):375-390. https://doi.org/10.3390/endocrines3030030
Chicago/Turabian StyleIto, Nobuaki. 2022. "Adult Presentation of X-Linked Hypophosphatemia" Endocrines 3, no. 3: 375-390. https://doi.org/10.3390/endocrines3030030