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Hypophosphatasia Treatment & Management

  • Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Dec 11, 2015
 

Medical Care

The FDA approved asfotase alfa (Strensiq) in 2015 as the first therapy for hypophosphatasia caused by a rare hereditary mutation in alkaline phosphatase gene. The drug may be used in addition to supportive care to decrease the morbidity associated with the disease. 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 older therapies.

Approval of asfotase alfa was based on four prospective, open-label studies involving 99 patients who developed hypophosphatasia in utero, as an infant, or as a juvenile. They received the drug for up to 6.5 years. Patients with either perinatal or infant onset of the disease who were treated with asfotase alfa showed improvement in overall survival, as well as ventilator-free survival. Ninety-seven percent of patients receiving the drug were alive at age 1 year compared with 42% of control patients selected from a natural history study group. The ventilator-free survival rates for both groups followed much the same pattern. Patients with juvenile-onset hypophosphatasia also experienced improved growth and bone health compared with patients in a natural history database.[7, 8]

 

One patient was reported with improved bone mineralization after starting enzyme replacement with recombinant asfotase alfa (ALP) from 1 day after birth.[9]

Enzyme replacement from birth in TNALP knockout mice using bone-targeted, recombinant human TNALP prevented the disease.[10] Targeted enzyme replacement therapy is currently being tested in humans.[7, 11, 12, 13]

Response to teriparatide treatment was seen in terms of decreased pain in 6 postmenopausal women, and no response was seen in 1 premenopausal woman.[14]

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.[15] The effects of bone marrow transplant in hypophosphatasia appear to be transient, as 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.[16]

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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.

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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.

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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.

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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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Contributor Information and Disclosures
Author

Horacio B Plotkin, MD, FAAP Chief Medical Officer, Retrophin, Inc; Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska College of Medicine

Horacio B Plotkin, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Received salary from Retrophin, Inc for management position.

Coauthor(s)

George A Anadiotis, DO Consulting Staff, Department of Pediatric Rehabilitation and Development, Division of Clinical and Biochemical Genetics, Emmanuel Children's Hospital

George A Anadiotis, DO is a member of the following medical societies: American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

James Bowman, MD Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical and Translational Research, College of American Pathologists

Disclosure: Nothing to disclose.

References
  1. Nishioka T, Tomatsu S, Gutierrez MA, et al. Enhancement of drug delivery to bone: characterization of human tissue-nonspecific alkaline phosphatase tagged with an acidic oligopeptide. Mol Genet Metab. 2006 Jul. 88(3):244-55. [Medline].

  2. Fraser D. Hypophosphatasia. Am J Med. 1957 May. 22(5):730-46. [Medline].

  3. 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].

  4. [Guideline] Jenny C. Evaluating infants and young children with multiple fractures. Pediatrics. 2006 Sep. 118(3):1299-303. [Medline].

  5. 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].

  6. 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.

  7. Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8. 366(10):904-13. [Medline].

  8. Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, et al. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2015 Nov 3. jc20153462. [Medline].

  9. Okazaki Y, Kitajima H, Mochizuki N, Kitaoka T, Michigami T, Ozono K. Lethal hypophosphatasia successfully treated with enzyme replacement from day 1 after birth. Eur J Pediatr. 2015 Oct 12. [Medline].

  10. Millan JL, Narisawa S, Lemire I, et al. Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res. 2008 Jun. 23(6):777-87. [Medline]. [Full Text].

  11. 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.

  12. Ozono K. [Biomineralization. Enzyme replacement therapy for hypophosphatasia]. Clin Calcium. 2014. 24(2):257-63. [Medline].

  13. Oda K, Kinjoh NN, Sohda M, Komaru K, Amizuka N. Biomineralization. Tissue-nonspecific alkaline phosphatase and hypophosphatasia. Clin Calcium. 2014. 24:233-239. [Medline].

  14. 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].

  15. 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].

  16. Plecko B, Stockler S. Vitamin B6 dependent seizures. Can J Neurol Sci. 2009. 36:S73-7. [Medline].

  17. van den Bos T, Handoko G, Niehof A, et al. Cementum and dentin in hypophosphatasia. J Dent Res. 2005 Nov. 84(11):1021-5. [Medline].

  18. Whyte MP. Enzyme defects and the skeleton. Primer on the metabolic bone diseases and disorders of mineral metabolism. 7th ed. 2008. 454-455.

  19. Whyte MP. Hypophosphatasia. The metabolic & molecular bases of inherited disease. 8th ed. 2001. 5313-29.

  20. Whyte MP, Kurtzberg J, McAlister WH, et al. Marrow cell transplantation for infantile hypophosphatasia. J Bone Miner Res. 2003 Apr. 18(4):624-36. [Medline].

 
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