- Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Luis O Rohena, MD more...
Until 2015, no effective drug therapy had been approved for hypophosphatasia. The FDA approved asfotase alfa as the first-ever therapy for hypophosphatasia caused by a rare hereditary mutation in alkaline phosphatase gene.[7, 8]
Enzyme replacement therapy helps to prevent bone demineralization.
Enzyme replacement that is a soluble glycoprotein composed of 2 identical polypeptide chains; each chain consists of the catalytic domain of human tissue–nonspecific alkaline phosphatase (TNSALP), the human immunoglobulin G1 Fc domain and a deca-aspartate peptide used as a bone-targeting domain. It is indicated for perinatal/infantile- and juvenile-onset hypophosphatasia.
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].
Fraser D. Hypophosphatasia. Am J Med. 1957 May. 22(5):730-46. [Medline].
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].
[Guideline] Jenny C. Evaluating infants and young children with multiple fractures. Pediatrics. 2006 Sep. 118(3):1299-303. [Medline].
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.
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].
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].
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].
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.
Ozono K. [Biomineralization. Enzyme replacement therapy for hypophosphatasia]. Clin Calcium. 2014. 24(2):257-63. [Medline].
Oda K, Kinjoh NN, Sohda M, Komaru K, Amizuka N. Biomineralization. Tissue-nonspecific alkaline phosphatase and hypophosphatasia. Clin Calcium. 2014. 24:233-239. [Medline].
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. 2005 Nov. 84(11):1021-5. [Medline].
Whyte MP. Enzyme defects and the skeleton. Primer on the metabolic bone diseases and disorders of mineral metabolism. 7th ed. 2008. 454-455.
Whyte MP. Hypophosphatasia. 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. 2003 Apr. 18(4):624-36. [Medline].