Hypophosphatasia Treatment & Management
- Author: Horacio Plotkin, MD, FAAP; Chief Editor: Bruce Buehler, MD more...
Medical Care
Currently, no medical therapy is available. Supportive care is generally aimed at decreasing the morbidity associated with hypophosphatasia. Regularly examine infants and children to check for evidence of increased intracranial pressure. Observe fractures closely. Adult pseudofractures may require orthopedic care to heal properly. A dentist should closely monitor all individuals with hypophosphatasia. Various treatments have been attempted, including zinc, magnesium, cortisone bisphosphonates, and plasma. The results have not been encouraging with these therapies.
Enzyme replacement from birth in TNALP knockout mice using bone-targeted, recombinant human TNALP prevented the disease.[7] Targeted enzyme replacement therapy is currently being tested in humans.[8, 9]
Response to teriparatide treatment was seen in terms of decreased pain in 6 postmenopausal women, and no response was seen in 1 premenopausal woman, suggesting that the effects may be related to improvement in osteoporosis rather than hypophosphatasia.[10]
Evidence also suggests that donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment to form TNSALP-replete osteoblasts, which may improve mineralization.[11] The effects of bone marrow transplant in hypophosphatasia are transient, and bone lesions may recur approximately 6 months after the transplantation. Nonsteroidal anti-inflammatory drugs have been used in patients with childhood hypophosphatasia with some clinical improvement, although more experience is warranted before this therapy can be recommended.
Enzyme replacement therapy with partially purified plasma enzyme was attempted, but with little clinical improvement.
Some success has been achieved in delivering functional TNSALP enzyme to bone.
Vitamin B-6 may be indicated to treat neonatal seizures.[12]
Surgical Care
Orthopedic surgical involvement may be necessary in patients with hypophosphatasia. Rachitic deformities and gait abnormalities require orthopedic evaluation. For them to heal completely, fractures, pseudofractures, and bone deformities may require rod placement. Patients may need neurosurgery for craniosynostosis.
Consultations
The skeletal involvement of hypophosphatasia requires consultation with an orthopedist. Patients with the infantile and childhood form should have regular follow-up appointments with their orthopedist. Evaluate adults for pseudofractures of the femur or stress fractures of the metatarsals. Refer all patients with any form of hypophosphatasia to a dental specialist. Construction of dentures may be necessary if the permanent teeth cannot be preserved. Patients should see a metabolic bone diseases specialist.
Diet
No special diet for hypophosphatasia is followed. Avoid vitamin and mineral supplements for rickets. The traditional defects of vitamin D metabolism are not present in hypophosphatasia, and excessive vitamin D can cause hypercalcemia and other side effects.
Activity
Gait difficulties may hamper activity in children. Although no distinct guidelines have been established, avoidance of contact sports and adequate protection of the teeth are advisable.
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Balasubramaniam S, Bowling F, Carpenter K, et al. Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5'-phosphate availability. J Inherit Metab Dis. 2010;Epub:[Medline].
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Girschick HJ, Mornet E, Beer M, Warmuth-Metz M, Schneider P. Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy. BMC Pediatr. Jan 2007;7:[Medline].
Rauch F, Greenberg C, Whyte MP, et al. The Bone Tissue Defect in Children with Hypophosphatasia: Histomorphometric Study. Proceedings of the 33 Annual ASBMR Meeting. 2011.
Millan JL, Narisawa S, Lemire I, et al. Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res. Jun 2008;23(6):777-87. [Medline]. [Full Text].
Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. Mar 8 2012;366(10):904-13. [Medline].
Kishnani PS, Rockman CR, Whyte MP et al. Hypophosphatasia: Enzyme Replacement Therapy (ENB-0040) Decreases TNSALP Substrate Accumulation and Improves Functional Outcome in Affected Adolescents and Adults. Proceedings of American College of Medical Genetics. 2012;303.
Gagnon C, Sims NA, Mumm S, et al. Lack of Sustained Response to Teriparatide in a Patient with Adult Hypophosphatasia. J Clin Endocrinol Metab. 2010;Epub:[Medline].
Cahill RA, Wenkert D, Perlman SA, et al. Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts. J Clin Endocrinol Metab. Aug 2007;92:2923-30. [Medline].
Plecko B, Stockler S. Vitamin B6 dependent seizures. Can J Neurol Sci. 2009;36:S73-7. [Medline].
van den Bos T, Handoko G, Niehof A, et al. Cementum and dentin in hypophosphatasia. J Dent Res. Nov 2005;84(11):1021-5. [Medline].
Whyte MP. Enzyme defects and the skeleton. In: Primer on the metabolic bone diseases and disorders of mineral metabolism. 7th ed. 2008:454-455.
Whyte MP. Hypophosphatasia. In: The metabolic & molecular bases of inherited disease. 8th ed. 2001:5313-29.
Whyte MP, Kurtzberg J, McAlister WH, et al. Marrow cell transplantation for infantile hypophosphatasia. J Bone Miner Res. Apr 2003;18(4):624-36. [Medline].
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