- Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Luis O Rohena, MD more...
Complications of the more severe forms of hypophosphatasia usually involve the respiratory system. Skeletal deformities can predispose an infant to respiratory compromise or pneumonia. In the infantile form, craniosynostosis can lead to increased intracranial pressure.
The perinatal form is considered lethal. The infantile form is believed to be fatal in approximately 50% of patients. Longevity studies have not been conducted for the infantile and childhood forms. Individuals with the adult and odontohypophosphatasic forms are believed to have normal lifespans.
Genetic counseling is important for all families who have affected children. A pedigree is essential, especially for the childhood, adult, or odontohypophosphatasic forms, which can have either autosomal dominant or recessive forms. Options for future pregnancies, such as prenatal testing for the perinatal form, should be discussed with parents.
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].