Hereditary Hypophosphatemic Rickets (HHR)

Hereditary hypophosphatemic rickets (HHR) is a group of genetic disorders where the kidneys lose too much phosphate in the urine. Low blood phosphate makes bones soft: in children this causes rickets (bowed legs, growth delay), and in adults it causes osteomalacia (bone pain, fractures). The commonest form is X-linked hypophosphatemia (XLH), caused by PHEX gene changes that raise a hormone called FGF23. Extra FGF23 tells the kidneys to waste phosphate and to make less active vitamin D, so the body cannot harden bone properly. HHR can also involve teeth (spontaneous dental abscesses), hearing (sometimes hearing loss), and skull sutures (craniosynostosis). Lifelong, team-based care by a metabolic bone specialist, dentist, orthopedist, and ENT is usually needed. Nature+3NCBI+3Endocrine+3

Hereditary hypophosphatemic rickets is a group of rare genetic disorders where the kidneys lose too much phosphate into the urine. Phosphate is essential for building strong bones and teeth. When phosphate stays low in the blood for a long time, the growing ends of bones cannot mineralize normally. In children this causes rickets (soft, deformed bones), and in adults it causes osteomalacia (poorly mineralized bone with pain and fractures). Most inherited forms are driven by too much action of a hormone called FGF23, which tells the kidneys to waste phosphate and to make less active vitamin D; a smaller group is FGF23-independent and is due to defects in kidney phosphate transporters. OUP Academic+2Journal of Molecular Endocrinology+2

Other names

Doctors and families may see several names that refer to the same clinical picture of low-phosphate rickets. Common synonyms include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR1 due to DMP1; ARHR2 due to ENPP1), and hereditary hypophosphatemic rickets with hypercalciuria (HHRH, due to SLC34A3). Older terms you might still encounter are “vitamin D-resistant rickets” and “familial hypophosphatemia.” PubMed+4NCBI+4PubMed+4

Types

FGF23-mediated (kidney wastes phosphate because FGF23 is too high or too active):

• XLH (PHEX mutations; X-linked dominant): the most common form worldwide. Nature

• ADHR (FGF23 mutations; autosomal dominant): FGF23 becomes resistant to breakdown and stays high. PubMed

• ARHR1 (DMP1 mutations; autosomal recessive): bone matrix signaling raises FGF23. PMC

• ARHR2 (ENPP1 mutations; autosomal recessive): low pyrophosphate and high FGF23; overlaps with infant arterial calcification (GACI). PMC+1

FGF23-independent (kidney transporters fail; FGF23 not elevated):

• HHRH (SLC34A3 mutations; autosomal recessive): phosphate wasting with high active vitamin D and hypercalciuria. PubMed

• SLC34A1-related disease (NaPi-IIa defects): can cause renal phosphate wasting, nephrocalcinosis, and rickets/osteomalacia in some patients. PMC+1

These categories help clinicians choose the right tests and treatment later. OUP Academic

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Causes

1. PHEX gene variants (XLH): Loss of PHEX function in bone raises circulating FGF23, so kidneys waste phosphate and make less active vitamin D. This is the most frequent inherited cause. Nature

2. FGF23 gain-of-function variants (ADHR): Mutations stabilize the FGF23 protein so it is not broken down; phosphate loss worsens especially when iron is low. PubMed+1

3. DMP1 loss-of-function (ARHR1): Defects in a bone matrix protein signal increase FGF23 production, lowering phosphate and vitamin D activation. PMC

4. ENPP1 loss-of-function (ARHR2): ENPP1 normally makes pyrophosphate. When it fails, soft-tissue calcifications can occur and FGF23 rises, causing hypophosphatemic rickets; some patients first present as infants with arterial calcification (GACI). PMC+1

5. SLC34A3 (NaPi-IIc) biallelic variants (HHRH): A kidney phosphate cotransporter is impaired; phosphate is lost, active vitamin D rises, and urine calcium is high (hypercalciuria). PubMed

6. SLC34A1 (NaPi-IIa) variants: Some patients with mutations have phosphate loss, kidney stones, nephrocalcinosis, and osteomalacia/rickets; the phenotype varies and may require two faulty copies for clear disease. PMC+1

7. KLOTHO (KL) variants (FGF23 resistance or signaling changes): Klotho partners with FGF receptors; human KL mutations perturb phosphate and vitamin D balance and can intersect with the FGF23 pathway. Junior Chamber International+1

8. GALNT3 variants (FGF23 processing): This enzyme O-glycosylates FGF23 to protect it from cleavage; disturbances can shift FGF23 bioactivity and alter phosphate. ScholarWorks

9. Modifier genes of bone matrix signaling: Experimental and cohort work shows that genes influencing bone-to-kidney signaling (e.g., FAM20C) can shift FGF23 biology and phosphate, contributing to hypophosphatemic rickets–like pictures in rare families. Journal of Molecular Endocrinology

10. Copy-number changes in PHEX region: Deletions or complex rearrangements that remove PHEX result in the same XLH mechanism—excess FGF23 and phosphate loss. PMC

11. Compound heterozygous DMP1 variants: Having two different harmful DMP1 variants can produce very early-onset ARHR1 with growth issues and severe rickets. OUP Academic

12. Novel ENPP1 splice or intronic variants: Recently reported ENPP1 defects expand the spectrum and remind clinicians to test ENPP1 when FGF23 is high and family history is recessive. Pediatric Endocrinology Journal

13. ENPP1 deficiency carriers with milder skeletal traits: Emerging data suggest even single-allele changes may subtly affect bone metabolism in some people, though full ARHR2 needs two alleles. OUP Academic

14. SLC34A3 phenotypic expansion: Families show variable age at presentation and severity, from childhood rickets to adult kidney stones with hypophosphatemia. OUP Academic

15. SLC34A1 infantile hypercalcemia spectrum: In some biallelic cases, very high active vitamin D, hypercalcemia, and phosphate wasting lead to rickets-like bone disease. MedlinePlus+1

16. Iron deficiency unmasking ADHR: In ADHR, iron deficiency can trigger or worsen phosphate wasting because it drives FGF23 production and processing abnormalities. PNAS

17. Rare KL-FGF23 axis disruptions (translocations/overexpression): Abnormalities in this axis can tilt phosphate handling and produce hypophosphatemic phenotypes. PNAS

18. Polygenic/undetermined inherited rickets: In some cohorts, no single mutation is found in PHEX/FGF23/DMP1/ENPP1/SLC34A3, suggesting undiscovered genes or combined small effects. Nature

19. Overlap with ABCC6/vascular calcification biology (research stage): Natural-history studies show shared pathways of ectopic mineralization with ENPP1 deficiency that can influence skeletal mineralization. OUP Academic

20. Newly reported SLC34A1 variants with early severe phenotype: Case reports continue to identify NaPi-IIa mutations that manifest early with phosphate wasting and bone disease. MDPI

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Symptoms

1. Bowed legs or knock knees: As children start standing and walking, poor mineralization near the knees leads to genu varum (bow-legs) or genu valgum (knock-knees). Frontiers

2. Short stature and slow growth: Long bones do not mineralize well at growth plates, so overall height can fall behind peers without treatment. OUP Academic

3. Waddling gait and delayed walking: Hip and leg deformities, plus muscle weakness, change the walking pattern and may delay milestones. Frontiers

4. Bone pain and tenderness: Poorly mineralized bone bends and micro-fractures easily, causing daily pain that may worsen with activity. PMC

5. Frequent fractures or “pseudofractures”: Adults develop Looser’s zones—thin lines in bone that look like cracks and hurt with weight-bearing. WJGNet

6. Dental abscesses in intact teeth: In XLH, enamel and dentin are poorly mineralized, so infection can start inside teeth even without obvious cavities. MDPI+1

7. Head shape changes or early suture fusion (craniosynostosis): Some children with XLH have early closure of skull sutures, sometimes needing neurosurgical care. PMC+1

8. Hearing problems, tinnitus, or vertigo: Both conductive and sensorineural hearing loss are reported, more often in adults with XLH. PMC+1

9. Enthesopathy (painful tendon/ligament insertions): Calcium builds up where tendons and ligaments attach to bone, causing stiffness and pain in adults. PMC

10. Early osteoarthritis: Abnormal bone alignment and enthesopathy can speed joint wear, leading to stiffness and reduced mobility. MDPI

11. Fatigue and reduced exercise tolerance: Chronic bone pain, muscle weakness, and deformity make daily tasks tiring. PMC

12. Muscle weakness: Low phosphate impairs muscle energy and can cause a myopathy pattern with difficulty climbing stairs or rising from the floor. OUP Academic

13. Spinal stenosis or back issues in adults: Enthesopathy and bone remodeling around the spine can contribute to pain and nerve compression in some. ScholarWorks

14. Kidney calcifications (especially with some treatments or in HHRH): Nephrocalcinosis can occur in XLH and is characteristic in HHRH due to high urine calcium. Frontiers+1

15. Headache or signs of raised intracranial pressure (with craniosynostosis): Watch for vomiting, papilledema, or eye movement changes. OUP Academic

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Diagnostic tests

A) Physical examination (bedside)

1. Growth and body proportion charting: Measuring height/length, weight, and limb proportions over time shows growth failure and limb deformity typical of rickets. OUP Academic

2. Gait observation and functional tests (chair-rise, stair climb): A waddling gait and difficulty rising suggest hip deformity and muscle weakness from chronic hypophosphatemia. PMC

3. Skeletal alignment checks (knees, wrists, ankles): Bowing, wrist flaring, and costochondral “rickety rosary” are classic cues to rickets during childhood. NCBI

4. Head and cranial suture exam: Abnormal head shape or palpable suture ridges raise suspicion for craniosynostosis in XLH. PMC

B) Manual/clinical maneuvers

5. Range-of-motion testing of hips/knees/ankles: Restricted motion reflects joint remodeling, enthesopathy, or osteoarthritis in older patients. MDPI

6. Tenderness to palpation over shins, ribs, and pelvis: Focal pain suggests pseudofractures or active rickets, guiding imaging. WJGNet

7. Hearing screen (whisper/bedside tuning fork, then audiology): A quick screen can detect conductive or sensorineural loss common in adults with XLH. OUP Academic

C) Laboratory & pathological tests

8. Serum phosphate (low for age): The core biochemical feature; children have higher normal ranges than adults, so age-specific ranges matter. NCBI

9. Serum calcium (often normal) and alkaline phosphatase (usually high in active rickets): These help separate rickets types and show bone turnover. NCBI

10. 1,25-dihydroxyvitamin D (calcitriol): Low/inappropriately normal in FGF23-mediated types (XLH/ADHR/ARHR); high in HHRH. Journal of Molecular Endocrinology+1

11. PTH (parathyroid hormone): Often normal or mildly high; helps rule in/out secondary hyperparathyroidism that can complicate the picture. StatPearls

12. FGF23 level (intact assay): Inappropriately high in FGF23-mediated disorders; helps distinguish these from transporter defects. Journal of Molecular Endocrinology

13. Renal phosphate handling (TmP/GFR): Calculated from blood and urine; shows reduced kidney reabsorption of phosphate. OUP Academic

14. Urine calcium and phosphate: High urine calcium suggests HHRH; ongoing phosphate wasting is common across types. PubMed

15. Genetic testing panels: Sequencing PHEX, FGF23, DMP1, ENPP1, SLC34A3, SLC34A1 (and related genes) confirms the type and guides family counseling. Nature

16. Iron studies in suspected ADHR: Low iron can unmask or worsen ADHR by altering FGF23 production/processing; checking ferritin and iron helps interpret relapses. PNAS

D) Electrodiagnostic tests

17. Electromyography (EMG): In chronic hypophosphatemia/osteomalacia, EMG can show a myopathic pattern that matches proximal muscle weakness. This helps when weakness is prominent or diagnosis is delayed. OUP Academic+1

18. Nerve conduction studies (select cases): Usually normal, but used to rule out neuropathy when patients present with pain, weakness, or gait issues not fully explained by bone disease. American Academy of Neurology

E) Imaging tests

19. X-rays of wrists/knees/long bones: In children, show classic rickets changes at metaphyses; in adults, look for Looser’s zones and deformities. NCBI+1

20. Dental panoramic films and targeted dental imaging: Reveal enlarged pulp chambers and structural enamel/dentin defects that explain spontaneous abscesses. ADA

(Additional studies are used when indicated—cranial CT/MRI for craniosynostosis/Chiari concerns; DXA or bone density adjuncts for osteomalacia burden; and renal ultrasound to screen for nephrocalcinosis—based on symptoms and lab findings.) OUP Academic+1

Non-pharmacological treatments

1) Multidisciplinary care pathway.
Description: People with HHR benefit from a coordinated team—metabolic bone specialist, pediatrician or internist, dentist, orthopedics, physiotherapy, ENT/audiology, neurosurgery when needed, and genetics. Regular visits track growth (children), pain, mobility, skeletal alignment, dental health, and hearing. Purpose: Reduce complications, detect problems early, and tailor therapy across life stages. Mechanism: Team care matches problems to the right specialist and times interventions around growth, surgery windows, and medication adjustments. Nature

2) Growth and gait-focused physiotherapy.
Description: PT builds strength, improves gait, preserves range of motion, and trains safe movement. Programs include low-impact strengthening, stretching of tight muscle groups, balance, and functional training (stairs, transfers). Purpose: Lessen pain and fatigue; improve endurance and daily function. Mechanism: Better muscle support and alignment reduce joint load and help compensate for osteomalacia-related weakness. X Linked Hypophosphatemia

3) Orthoses and bracing during growth.
Description: Guided bracing and orthoses (e.g., knee-ankle-foot orthoses) support alignment while medical therapy works. Purpose: Limit progression of varus/valgus deformity, especially during rapid growth. Mechanism: External support redistributes forces across growth plates and joints, buying time until medical treatment improves mineralization or until a guided-growth procedure is possible. PMC

4) Guided-growth (hemiepiphysiodesis) timing strategy.
Description: When deformity persists despite medical therapy, temporary tethering of one side of the growth plate can gradually correct alignment. Purpose: Correct knee valgus/varus and leg length difference with less invasive surgery in growing children. Mechanism: Asymmetric growth guidance allows the untethered side to grow more, slowly straightening the limb. MDPI+1

5) Pre- and postoperative rehabilitation.
Description: When osteotomy or other surgery is needed, targeted prehab and post-op rehab speed recovery and protect alignment. Purpose: Optimize surgical outcomes and mobility. Mechanism: Strength and range of motion support bone healing and joint mechanics after correction. Journal Bone Fragility

6) Dental prevention program.
Description: Very early dental visits; high-fluoride hygiene; fissure sealants; prompt endodontic care; and infection control plans reduce abscesses and tooth loss. Purpose: Protect teeth and avoid recurrent antibiotics or extractions. Mechanism: Strengthening enamel/dentin surfaces and sealing entry points lowers risk of pulp infections in hypomineralized teeth. PMC+1

7) ENT surveillance and hearing support.
Description: Baseline and periodic audiology; early hearing-aid fitting if needed; consideration of middle-ear or cochlear surgery in selected cases. Purpose: Maintain communication, learning, and safety. Mechanism: Amplification and surgical options compensate for conductive or sensorineural loss that can appear with age. BioMed Central+1

8) Neurosurgical evaluation for craniosynostosis.
Description: Monitor head shape, sutures, and signs of raised intracranial pressure; operate when indicated. Purpose: Protect brain development and prevent headaches/vision problems. Mechanism: Suture release and cranial remodeling restore skull growth pathways. PMC

9) Pain self-management and pacing.
Description: Activity pacing, sleep hygiene, heat/cold, and cognitive behavioral strategies help chronic bone/joint pain. Purpose: Reduce pain impact while limiting medication needs. Mechanism: Graded activity and coping skills lessen central sensitization and mechanical stress on painful structures. PMC

10) Fall-risk reduction.
Description: Home safety checks, balance training, and vision/hearing optimization cut fall risk. Purpose: Prevent fractures and head injury in osteomalacia. Mechanism: Environmental changes and better sensory input reduce instability. PMC

11) Genetic counseling and family testing.
Description: Discuss inheritance (often X-linked dominant), options for testing relatives, and pregnancy planning. Purpose: Enable early diagnosis and timely treatment for affected family members. Mechanism: Identifying carriers/affected individuals before symptoms appear allows earlier care. NCBI

12) School/workplace accommodations.
Description: Flexibility for rest breaks, ergonomic seating, and PE modifications. Purpose: Support participation and reduce pain flares. Mechanism: Reducing repetitive load and allowing pacing improves function. PMC

(Additional non-pharmacological measures often included by specialist teams overlap with the items above; the key is individualized, age-aware planning.) Nature

Drug treatments

For each: long description (~150 words), class, typical dosing/time (illustrative only; follow label/clinician advice), purpose, mechanism, key side effects.
Important: This is general education, not personal medical advice.

1) Burosumab (CRYSVITA®).
Description: Burosumab is a monoclonal antibody that binds and blocks FGF23. It is FDA-approved to treat XLH in adults and children ≥6 months. It raises serum phosphate, improves tubular phosphate reabsorption, and increases 1,25-dihydroxyvitamin D, helping bones mineralize. Conventional oral phosphate and active vitamin D must be stopped one week before starting. Doses are weight-based and adjusted to keep serum phosphorus in the low-to-mid normal range for age while avoiding hyperphosphatemia. Class: FGF23-blocking antibody (biologic). Dosing/Time: Subcutaneous injection at intervals per label; pediatric and adult dosing differ; titrate by labs. Purpose: Core disease-modifying therapy for XLH. Mechanism: Neutralizes excess FGF23 signaling that drives renal phosphate wasting. Side effects: Injection site reactions, headache, tooth abscess, hypersensitivity; monitor phosphorus, calcium, and renal function per label. FDA Access Data+2FDA Access Data+2

2) Calcitriol (Rocaltrol®).
Description: Calcitriol is active vitamin D. In “conventional therapy,” calcitriol plus divided oral phosphate doses improve rickets/osteomalacia when burosumab is not used. Calcitriol enhances intestinal calcium/phosphate absorption but must be balanced to avoid hypercalcemia or nephrocalcinosis; frequent labs are essential. Class: Vitamin D analog (active 1,25-(OH)₂D). Dosing/Time: Often 0.25–0.75 mcg/day in divided doses in adults as a starting range in legacy protocols; exact dosing is individualized and guided by labs and specialist oversight. Purpose: Improve mineralization when FGF23 blockade is unavailable/inappropriate. Mechanism: Boosts intestinal mineral absorption and suppresses secondary hyperparathyroidism. Side effects: Hypercalcemia, hypercalciuria, nephrocalcinosis; requires careful monitoring. FDA Access Data+1

3) Oral phosphate salts (e.g., neutral phosphate preparations).
Description: Divided oral phosphate can raise serum phosphate transiently and support rickets healing in conventional regimens with calcitriol. Doses are split 3–5 times daily to reduce GI side effects. Many products are OTC or listed in DailyMed; IV phosphate is reserved for acute hypophosphatemia when oral is not possible. Class: Phosphate replacement. Dosing/Time: Individualized; frequent, small oral doses during waking hours; IV only for acute inpatient use. Purpose: Support bone mineralization in conventional therapy. Mechanism: Replaces lost phosphate; partially overcomes renal wasting. Side effects: Diarrhea, abdominal pain; with over-replacement: hyperphosphatemia, hypocalcemia, calcifications (more likely without calcitriol guidance). DailyMed+2FDA Access Data+2

4) Thiazide diuretics (e.g., hydrochlorothiazide).
Description: Some patients on conventional therapy develop hypercalciuria or nephrocalcinosis. Thiazides can reduce urinary calcium excretion and are sometimes used adjunctively under specialist care. Class: Thiazide diuretic. Dosing/Time: Hypertension-range doses are used clinically; exact dosing is individualized. Purpose: Lower urine calcium to protect kidneys when calcitriol is needed. Mechanism: Increases distal tubular calcium reabsorption. Side effects: Low potassium/sodium, photosensitivity, gout flare, glucose and lipid changes—labs and electrolytes must be monitored. FDA Access Data+1

5) Cinacalcet (Sensipar®) for tertiary hyperparathyroidism (select cases).
Description: Long-term high phosphate/calcitriol exposure in conventional therapy can stimulate the parathyroid glands. Rarely, tertiary hyperparathyroidism develops and may require cinacalcet to control PTH and calcium while planning definitive care. Class: Calcimimetic. Dosing/Time: Titrated every 2–4 weeks per label; must be taken with food. Purpose: Reduce PTH and calcium when overactive parathyroid persists. Mechanism: Sensitizes calcium-sensing receptor to suppress PTH. Side effects: Nausea, hypocalcemia, rare seizures—close calcium monitoring is essential. (Use in XLH is off-label; indication is per FDA label for other hyperparathyroid states.) FDA Access Data+1

6) Analgesics (stepwise, short-term).
Description: For flares of bone or joint pain, short courses of acetaminophen or NSAIDs may help, while the main therapy targets mineralization. Class: Analgesic/NSAID. Dosing/Time: As per label; lowest effective dose for shortest time. Purpose: Symptom control. Mechanism: Central analgesia (acetaminophen) or COX inhibition (NSAIDs). Side effects: Liver toxicity risk (acetaminophen overuse); GI, renal, and CV risks (NSAIDs). (General labels apply; not disease-specific.) PMC

7) Antibiotics for dental infections (when indicated).
Description: Spontaneous dental abscesses may require prompt antibiotics plus endodontic care. Choice follows standard dental infection guidelines. Class: Antibacterial. Dosing/Time: Per agent/label and dentist’s plan. Purpose: Control infection, protect teeth. Mechanism: Eradicate oral pathogens while definitive dental therapy is arranged. Side effects: Drug-specific; antibiotic stewardship applies. PMC

8) Anti-resorptives (generally not routine for XLH).
Description: Classic osteoporosis drugs (e.g., bisphosphonates) are not standard XLH therapy and may worsen bone pain if osteomalacia is active. They are reserved for specific adult scenarios after expert review. Class: Bisphosphonate/anti-resorptive. Purpose/Mechanism/Side effects: Case-specific. Note: Prioritize correcting mineralization defect first. PMC

9) Burosumab in adults with fractures/pseudofractures.
Description: Contemporary adult guidance favors burosumab when adults have fractures, pseudofractures, or significant symptoms, because outcomes are superior to no therapy and often better than conventional therapy. Class/Purpose/Mechanism: As above. Side effects: As above. OUP Academic

10) Transition-age management (adolescent → adult).
Description: Medicines and monitoring often need retuning as growth stops and adult risks rise (enthesopathy, pain, hearing issues). A structured hand-off avoids gaps in therapy. Class: Care process including drug retitration. Purpose: Keep benefits, minimize risks. Mechanism: Planned dose/interval adjustments and lab schedules. PMC

Important label rule when starting burosumab: stop oral phosphate and active vitamin D analogs ≥1 week before first burosumab dose; labs must be monitored to avoid hyperphosphatemia. FDA Access Data

Dietary molecular supplements

1) Cholecalciferol (vitamin D3) at nutritional doses.
Supports general vitamin D status alongside disease-specific therapy; avoid “mega-doses.” The aim is normal—not high—25-OH vitamin D, under clinician guidance. Mechanism: improves baseline calcium/phosphate absorption. PMC

2) Calcium (only if deficient).
Routine high calcium is not universal in XLH; supplementation is individualized to labs and therapy. Excess can worsen nephrocalcinosis, especially with calcitriol; follow specialist advice. Mechanism: substrate for mineralization. PMC

3) Magnesium (if low).
Correcting hypomagnesemia helps PTH and vitamin D metabolism and may reduce cramps. Use lab-guided dosing to avoid diarrhea. Mechanism: cofactor in vitamin D activation and PTH signaling. PMC

4) Phosphate in food vs. pills.
Dietary phosphate alone rarely corrects XLH because kidneys waste phosphate; medical therapy is primary. Avoid assuming “more dietary phosphate” will fix the disease. Mechanism: dietary input is overshadowed by renal loss. PMC

5) Fluoride varnish/topical agents (dental).
Topical fluoride supports enamel strength and lowers caries/abscess risk; follow dentist schedule. Mechanism: increases enamel resistance to acid. PMC

6) Omega-3s (adjunct for pain).
May help general musculoskeletal comfort in some patients; not disease-modifying. Mechanism: modest anti-inflammatory effects. Use food-first (fish) and clinician-approved dosing. PMC

7) Protein adequacy.
Adequate protein supports bone matrix formation and wound healing around surgeries. Mechanism: provides amino acids for collagen and muscle. PMC

8) Hydration strategy.
Good hydration supports kidney health, especially when on conventional therapy with calcitriol/phosphate. Mechanism: lowers urinary supersaturation risks. PMC

9) Micronutrient balance (B-complex, K).
General balanced intake supports bone turnover enzymes; avoid megadoses. Mechanism: cofactor roles in matrix formation. PMC

10) Avoid “bone booster” claims.
Supplements cannot replace burosumab or properly dosed calcitriol/phosphate. Beware unproven “stem-cell boosters” or high-dose vitamin regimens. Nature

Immunity-booster / regenerative / stem-cell drugs

There are no FDA-approved stem-cell or “regenerative” drugs for treating hereditary hypophosphatemic rickets itself. The only U.S. FDA-approved disease-modifying medicine for XLH is burosumab (CRYSVITA); calcitriol is FDA-approved for other indications and used in conventional therapy, while oral phosphate products are nutritional or replacement agents. Be cautious with any clinic offering “stem-cell” injections for XLH. FDA Access Data+1

If severe hypophosphatemia occurs in hospital settings when oral intake is impossible, IV potassium phosphates can be used to correct phosphorus—this is for acute correction, not chronic XLH control. It requires cardiac, potassium, calcium, and renal monitoring per FDA label. FDA Access Data

Bottom line: For XLH/HHR, stick to guideline-supported therapy (burosumab or specialist-guided conventional therapy). Avoid unapproved “regenerative” claims. Nature

Surgeries (what is done and why)

1) Guided-growth (temporary hemiepiphysiodesis).
Procedure: Small plates/screws tether one side of the growth plate to gradually correct knee valgus/varus. Why: Correct alignment during growth with less invasive surgery. MDPI+1

2) Corrective osteotomy.
Procedure: Cut and realign bone, sometimes with external/internal fixation, to correct multi-apical deformities once growth is limited or deformity is severe. Why: Restore mechanical axis, relieve pain, and improve function. Journal Bone Fragility+1

3) Neurosurgical craniosynostosis repair.
Procedure: Suture release and cranial vault remodeling. Why: Treat raised intracranial pressure and skull deformity in XLH-related craniosynostosis. PMC

4) Dental endodontic and restorative procedures.
Procedure: Early root canal therapy of vulnerable teeth, sealants, and restorations to prevent recurrent abscess. Why: Preserve teeth and prevent infection in hypomineralized dentin. PMC

5) Joint replacement (select adults).
Procedure: Hip or knee arthroplasty for advanced degenerative changes. Why: Restore mobility and relieve pain when conservative measures fail. BioMed Central

Preventions

1. Early diagnosis in at-risk families through genetic counseling/testing. NCBI

2. Regular follow-up with a metabolic bone specialist across life stages. Nature

3. Consistent dental hygiene and early dental care to prevent abscesses. PMC

4. Audiology checks in adulthood, earlier if symptoms appear. PMC

5. Monitor growth, limb alignment, and gait in children; act early if deformity persists. PMC

6. Use guideline-backed medical therapy (burosumab or conventional) rather than unproven “regenerative” products. Nature

7. Plan surgeries at the right growth window to maximize benefit and minimize re-operation. MDPI

8. Educate on pacing and safe activity to reduce pain flares and falls. PMC

9. Optimize vitamin D status and hydration under clinician guidance. PMC

10. Structured transition plan from pediatric to adult services. PMC

When to see a doctor

See your specialist promptly for new or worsening bone pain, limping, sudden deformity, suspected fracture/pseudofracture, recurrent dental abscess, headaches or vision changes (possible craniosynostosis issues), or new hearing problems (tinnitus, fullness, reduced hearing). Seek urgent care for severe pain after a fall, fever with dental swelling, or signs of high calcium (confusion, excessive thirst/urination) if on calcitriol—because dosing may need adjustment. PMC+2PMC+2

What to eat

Eat: a balanced diet with adequate protein; plenty of fruits/vegetables; routine, not mega-dose, vitamin D; and dentist-endorsed topical fluoride as advised. Keep well hydrated to support kidneys—especially on calcitriol. Avoid: “high-dose miracle” vitamin regimens, unregulated “stem-cell boosters,” and self-directed phosphate loading (the kidneys still waste phosphate; medical therapy is primary). Limit frequent cola intake and ultra-processed foods if they displace nutrient-dense foods. Always coordinate supplements and diet with your metabolic bone team. PMC+2PMC+2

FAQs

1) Is XLH the same as “vitamin D deficiency” rickets?
No. In XLH, kidneys waste phosphate due to high FGF23, so simple vitamin D alone cannot fix it. Nature

2) What is the main modern treatment?
Burosumab, an antibody to FGF23, is FDA-approved for XLH and targets the root mechanism. FDA Access Data

3) Do I stop phosphate and calcitriol if I start burosumab?
Yes—per FDA label, stop at least one week before the first dose; your team will monitor labs. FDA Access Data

4) If I cannot access burosumab, is there another option?
Conventional therapy uses divided oral phosphate with calcitriol under close monitoring. PMC

5) Why so many blood/urine tests?
To balance minerals and protect kidneys (avoid hypercalcemia/hyperphosphatemia). FDA Access Data

6) Can dental abscesses be prevented?
Risk drops with early dental care, fluoride, sealants, and rapid treatment of any pulpitis. PMC

7) Will hearing always get worse?
Not always. Adults can develop hearing loss, but ENT care (aids, surgery) often helps. OUP Academic

8) Does surgery replace medicine?
No. Surgery corrects alignment or skull issues; medicine treats the mineral problem. Both may be needed. PMC

9) Is craniosynostosis common?
It is more frequent in XLH than in the general population and usually involves the sagittal suture. Pediatric Endocrine Society

10) Are stem-cell injections a cure?
No FDA-approved stem-cell therapies exist for XLH; be cautious about unproven claims. Nature

11) Do adults benefit from treatment?
Yes—adult guidance supports treating symptomatic adults; burosumab is often recommended when fractures or pseudofractures are present. OUP Academic

12) Can XLH affect pregnancy?
Care is individualized; coordinate with your high-risk obstetrics and bone specialist teams for medication timing and monitoring. Nature

13) What about exercise?
Low-impact, strength and balance-focused programs help mobility and reduce pain flares. X Linked Hypophosphatemia

14) Are thiazides used for kidney protection?
Sometimes, to reduce urine calcium during calcitriol therapy; dosing and labs are specialist-guided. FDA Access Data

15) Where can I read reliable overviews?
GeneReviews, Endocrine Society patient pages, and updated clinical recommendations provide trustworthy detail. NCBI+2Endocrine+2

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Last Updated: October 02, 2025.

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