Osteoporosis International

, Volume 29, Issue 2, pp 511–515 | Cite as

Asfotase alfa treatment for 1 year in a 16 year-old male with severe childhood hypophosphatasia

  • S. A. BowdenEmail author
  • B. H. Adler
Case Report


We describe the clinical outcome of asfotase alfa therapy in a 16-year-old boy with severe childhood hypophosphatasia (HPP), who began therapy at age 15 years. The patient was diagnosed with HPP at age 2 years when he presented with genu varum and premature loss of primary teeth. He had a history of multiple fractures requiring 16 orthopedic surgeries with rod and pin placement in his lower extremities. He had chronic skeletal pain and used cane to ambulate with great difficulty. His height Z score at age 15 years was − 5. He had severe scoliosis and deformity of both legs. Bone radiograph showed hypomineralization and characteristic “tongues” of radiolucency in the distal radius and ulna. His serum alkaline phosphatase level was stable, with elevated serum pyridoxal 5′-phosphate and urine phosphoethanolamine, consistent with HPP. He was started on asfotase alfa 2 mg/kg given subcutaneously thrice weekly. He had marked clinical improvement in mobility with no report of pain after 3 months of treatment. At 6 month, he walked without cane and participated in outdoor activities with peers. Bone radiograph at 6 months showed striking improvement in previous radiolucent areas. At 9 months, his annualized growth velocity was 9.5 cm/year, while growth velocity of arm span was 12 cm/year. However, at 12 months, he was noted to have worsening scoliosis from 60 degrees before therapy to 110 degrees, with a slight decrease in height, necessitating a spinal fusion surgery. In conclusion, treatment with asfotase alfa significantly improved physical function, pain, overall quality of life, and skeletal radiographic findings in this patient. Close monitoring for progression of scoliosis in adolescents with HPP treated with asfotase alfa is recommended.


Asfotase alfa Hypophosphatasia Scoliosis Short stature 





tissue-nonspecific isoenzyme of alkaline phosphatase


inorganic pyrophosphate


pyridoxal 5′-phosphate





The authors thank Melody Davis, PhD, for her critical review of the manuscript.

Compliance with ethical standards

Conflicts of interest



The patient’s parent provided written informed consent for publication of this case report.

Supplementary material

198_2017_4267_MOESM1_ESM.docx (881 kb)
ESM 1 (DOCX 881 kb)


  1. 1.
    Whyte MP (2017) Hypophosphatasia: an overview for 2017. Bone 102:15–25CrossRefGoogle Scholar
  2. 2.
    Whyte MP (2016) Hypophosphatasia—aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 12(4):233CrossRefGoogle Scholar
  3. 3.
    Caswell AM, Whyte MP, Russell RGG (1991) Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate: clinical and laboratory aspects. Crit Rev Clin Lab Sci 28(3):195–232CrossRefGoogle Scholar
  4. 4.
    Whyte MP, Zhang F, Wenkert D, McAlister WH, Mack KE, Benigno MC et al (2015) Hypophosphatasia: validation and expansion of the clinical nosology for children from 25years experience with 173 pediatric patients. Bone 75:229–239CrossRefGoogle Scholar
  5. 5.
    Wenkert D, McAlister WH, Coburn SP, Zerega JA, Ryan LM, Ericson KL et al (2011) Hypophosphatasia: nonlethal disease despite skeletal presentation in utero (17 new cases and literature review). J Bone Miner Res 26(10):2389–2398CrossRefGoogle Scholar
  6. 6.
    Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D et al (2012) Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med 366(10):904–913CrossRefGoogle Scholar
  7. 7.
    Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A et al (2016) Asfotase alfa treatment improves survival for perinatal and infantile hypophosphatasia. J Clin Endocrinol Metab 101(1):334–342CrossRefGoogle Scholar
  8. 8.
    Whyte MP, Madson KL, Phillips D, Reeves AL, McAlister WH, Yakimoski A, et al (2016) Asfotase alfa therapy for children with hypophosphatasia. JCI Insight 1(9):e85971.
  9. 9.
    Kishnani PS, Madson KL, Whyte MP, Gayron M, Fujita K, Rockman-Greenberg C (2016) Biochemical and physical function outcomes in adolescents and adults with hypophosphatasia treated with asfotase alfa for up to 4 years: interim results from a phase II study. In: Presented at ENDO 2016, Boston, Massachusetts, 1–4 April 2016 Google Scholar
  10. 10.
    Whyte MP, Wenkert D, Zhang F (2016) Hypophosphatasia: natural history study of 101 affected children investigated at one research center. Bone 93:125–138CrossRefGoogle Scholar
  11. 11.
    Whyte MP (2000) Hypophosphatasia. The genetics of osteoporosis and metabolic bone disease, Humana Press, Totowa, p. 335–356.
  12. 12.
    Abbassi V (1998) Growth and normal puberty. Pediatrics 102(Supplement 3):507–511PubMedGoogle Scholar
  13. 13.
    Collins MT (2006) Spectrum and natural history of fibrous dysplasia of bone. J Bone Miner Res 21(S2).
  14. 14.
    Whyte MP, Kurtzberg J, McAlister WH, Mumm S, Podgornik MN, Coburn SP et al (2003) Marrow cell transplantation for infantile hypophosphatasia. J Bone Miner Res 18(4):624–636CrossRefGoogle Scholar
  15. 15.
    Arun R, Khazim R, Webb JK, Burn J (2005) Scoliosis in association with infantile hypophosphatasia: a case study in two siblings. Spine 30(16):E471–E4E6CrossRefGoogle Scholar
  16. 16.
    Millán JL, Whyte MP (2016) Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int 98(4):398–416CrossRefGoogle Scholar
  17. 17.
    Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA et al (2011) Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab 96(10):3160–3169CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2017

Authors and Affiliations

  1. 1.Division of Endocrinology, Department of PediatricsNationwide Children’s Hospital/The Ohio State University College of MedicineColumbusUSA
  2. 2.Department of RadiologyNationwide Children’s Hospital/The Ohio State University College of MedicineColumbusUSA

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