Table 10.

Treatment of Manifestations in Individuals with Hypophosphatasia

Manifestation/ConcernTreatmentConsiderations/Other
Respiratory
compromise
  • Respiratory support per pulmonologist
  • Asfotase alfa ERT (see Table 9) has been shown to improve survival & pulmonary function.
Comfort care & supportive mgmt of infants w/perinatal (severe) type remains an option for those w/o access to ERT.
Calcium
homeostasis /
Bone health 		Mgmt per endocrinologist to optimize bone homeostasis & avoid exacerbating treatmentsMgmt of calcium homeostasis can further be complicated by recalcitrant hypercalcemia/ hypercalciuria, & optimal mgmt remains unclear: hypercalcemia/ hypercalciuria is typically resistant to hydration & furosemide treatment, & bisphosphonates would be contraindicated (see Agents/Circumstances to Avoid).
Asfotase alfa ERT (See Table 9.)
  • Physical medicine & rehab, PT, & OT to optimize mobility & autonomy
  • Low-impact physical activity & exercise
Supervision by physician specialist familiar w/hypophosphatasia is suggested.
Adults: calcium & vitamin D supplementation may prevent secondary hyperparathyroidism.This should only be pursued w/close monitoring by physician specialist familiar w/hypophosphatasia.
Fractures
  • Mgmt of primary & secondary skeletal manifestations per orthopedist
  • Internal fixation has been suggested as optimal mgmt.
  • Consider foot orthotics for tarsal fractures & pseudofractures in adults.
Pseudofractures & stress fractures are difficult to manage.
Bone pain &
osteomalacia 		Adults: Teriparatide may improve pain, mobility, & fracture repair. 1
  • Teriparatide ↑s production of TNSALP in osteoblasts. To date, there are no prospective studies or clinical trials. Improvement in biochemical markers & bone mineral density have been mixed. 2
  • Teriparatide is contraindicated in children (see Agents/Circumstances to Avoid).
  • Pain mgmt
  • NSAIDs
Bisphosphonates are contraindicated (see Agents/Circumstances to Avoid).
Osteoarthritis May respond to NSAIDs
Craniosynostosis Mgmt per neurosurgeon to monitor & manage complications incl:
  • Intracranial hypertension
  • Indication for surgical release
Craniosynostosis in those w/infantile type is variable.
Kidney disease Mgmt per nephrologist to monitor calcium homeostasis & assess for nephrocalcinosis
Seizures & myopathy
  • Mgmt per neurologist to prophylactically or prospectively treat seizures & manage myopathy
  • Seizures may respond to treatment w/vitamin B6 (pyridoxine).
PLP is one of the natural substrates of ALP; PLP deficiency in CNS may ↓ seizure threshold by ↓ing neurotransmitter synthesis.
Dental complications Pediatric & adult dentistry to preserve primary dentition (to support nutrition) & to preserve or replace secondary dentition.By age 1 yr
Family support
& resources 		Psychological support & social work supportThe involvement of multiple specialists treating complex interrelated medical issues mandates case mgmt & social work support.

ALP = alkaline phosphatase; CNS = central nervous system; ERT = enzyme replacement therapy; NSAIDs = nonsteroidal anti-inflammatory drugs; OT = occupational therapy; PLP = pyridoxal phosphate; PT = physical therapy; TNSALP = alkaline phosphatase, tissue-nonspecific isozyme

1.
2.

From: Hypophosphatasia

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