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Clinical snapshot

In a natural history study of patients ≤5 years of age with hypophosphatasia (HPP)1:

61% (19/31) of patients with hypophosphatasia had craniosynostosis
Data from a noninterventional, retrospective chart review study designed to understand the natural history of 48 patients with severe perinatal- and infantile-onset hypophosphatasia ≤5 years of age.1

Neurologic manifestations are among the most critical for patients with hypophosphatasia.2-5

In hypophosphatasia, skeletal deformities may include craniosynostosis, which can lead to2,3

Increased intracranial pressure
Intracranial hemorrhage
Optic nerve damage
Multiple cranial surgeries

Vitamin B6–responsive seizures can predict a poor outcome.2,5

In addition to its role in bone mineralization, alkaline phosphatase (ALP) dephosphorylates pyridoxal 5’-phosphate (PLP, or vitamin B6) into pyridoxal (PL), allowing it to cross the plasma membrane into the central nervous system (CNS). Within the CNS, PL is rephosphorylated into PLP. Intracellular PLP is involved in neurotransmitter synthesis (eg, gamma aminobutyric acid [GABA], dopamine, serotonin).2,6
In patients with hypophosphatasia, PLP deficiency in the CNS can cause fatal vitamin B6–responsive seizures2,7,8

In infants with hypophosphatasia, vitamin B6–responsive seizures often lead to a fatal outcome.1,2,5

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  1. Whyte MP, Leung E, Wilcox W, et al; for Study 011-10 Investigators. Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms. Poster presented at: 2014 Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; May 3-6, 2014; Vancouver, BC.
  2. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388.
  3. Collmann H, Mornet E, Gattenlöhner S, Beck C, Girschick H. Neurosurgical aspects of childhood hypophosphatasia. Childs Nerv Syst. 2009;25(2):217-223.
  4. 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;33(3):25-33.
  5. Baumgartner-Sigl S, Haberlandt E, Mumm S, et al. Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene. Bone. 2007;40(6):1655-1661.
  6. Sebastián-Serrano Á, de Diego-García L, Martínez-Frailes C, et al. Tissue-nonspecific alkaline phosphatase regulates purinergic transmission in the central nervous system during development and disease. Comput Struct Biotechnol J. 2015;13:95-100.
  7. Whyte MP. Hypophosphatasia: nature’s window on alkaline phosphatase function in humans. In: Bilezikian JP, Raisz LG, Martin TJ, eds. Principles of Bone Biology. Vol 2. 3rd ed. San Diego, CA: Academic Press; 2008:1573-1598.
  8. Whyte MP. Hypophosphatasia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 4. 8th ed. New York, NY: McGraw-Hill; 2001:5313-5329.