Asfotase alfa treatment for 1 year in a 16 year-old male with severe childhood hypophosphatasia
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.
KeywordsAsfotase alfa Hypophosphatasia Scoliosis Short stature
tissue-nonspecific isoenzyme of alkaline phosphatase
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.
- 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. https://doi.org/10.1172/jci.insight.85971
- 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
- 11.Whyte MP (2000) Hypophosphatasia. The genetics of osteoporosis and metabolic bone disease, Humana Press, Totowa, p. 335–356. https://doi.org/10.1007/978-59259-033-9_18
- 13.Collins MT (2006) Spectrum and natural history of fibrous dysplasia of bone. J Bone Miner Res 21(S2). https://doi.org/10.1359/jbmr.06s219
- 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