Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Neonatal and Pediatric Hereditary Hypophosphatasia (HPP) Treated with Asfotase Alfa - Two Varied Presentations (#402)

Gnanagurudasan Prakasam 1 2 , Chandini Murali 3 4 5
  1. Sutter Institute of Medical Research, Sutter Health, Sacramento, CA, USA
  2. SUTTER MEDICAL CENTER, SACRAMENTO, SACRAMENTO, CA, United States
  3. Pediatric Endocrinology, Center of Excellence In Diabetes and Endocrinology, Sacramento, CA, USA
  4. Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
  5. School of Public Health, University of Sydney, Sydney, NSW, Australia

HPP is a loss-of-function mutation in ALPL gene, responsible for tissue-nonspecific alkaline phosphatase. Clinically, HPP presents as rickets with severe lack of bone mineralization with a low alkaline phosphatase level.

Pre-adolescent HPP: 11-year old female presented with significant short-stature(-5SD), poor dentition, waddling and painful gait. Diagnosis of HPP was based on bony malformations including chest deformity, low Bone Mineral Density(BMD) of SPINE with z-score - 3.9 (Feb 2014), bone pain, low Alkaline Phosphatase and ALPL Gene-Mutation.664a7a9a5a3e2-ALPL+mutation.PNG

Child was started on Asfotase-Alfa. Height change from -5SD, reached a final height of 148.3cm(-2 SD) and started college in 2023. BMD improved from -3.9SD to -1.9SD. Dental problems resolved, walking and driving with normal puberty explains her improved quality-of-life over 10years.

664a7a9a5a3e2-Growth+chart.PNG

Neonatal HPP: A full term child with prenatal scans with long-bone fractures raised concern for Osteogenesis imperfecta. However, alkaline phosphatase (ALP) at birth was <11 U/L, and vitamin B6 was elevated >250 ng/mL. Calcium, 25-OH vitamin D, and urine phosphoethanolamine were normal. A genetics panel for HPP confirmed two pathogenic autosomal recessive mutations on the ALPL gene. Treatment with asfotase alfa 3 mg/kg three times weekly was started on 2nd day of life. The clinical course was complicated by prolonged mechanical ventilator need, seizure-event shortly after birth, EEG demonstrating epileptogenic potential in the bitemporal cortical regions was started on Levetiracetam, possible craniosynostosis with mild-to-moderate ventriculomegaly, and minimal grade 1 medullary nephrocalcinosis. Bone mineralization was monitored via skeletal surveys, and changes were measured using the Radiographic Global Impression of Change (RGI-C) and the Rickets Scoring Scale (RSS). Due to the need for neonatal tracheostomy for persistent ventilatory requirement, child was transferred to a major academic center while on asfotase alfa

Conclusion: Awareness that treatment options for rare genetic bone diseases has improved survival and quality-of-life for patients suffering from these debilitating diseases.

  1. Scott, L.J. Asfotase Alfa: A Review in Paediatric-Onset Hypophosphatasia. Drugs 76, 255–262 (2016). https://doi.org/10.1007/s40265-015-0535-2
  2. Scott, L.J. Asfotase Alfa in Perinatal/Infantile-Onset and Juvenile-Onset Hypophosphatasia: A Guide to Its Use in the USA. BioDrugs 30, 41–48 (2016). https://doi.org/10.1007/s40259-016-0161-x
  3. Jaswanthi N, Sindhu R, Nimmy P, Prabu D, RajMohan M, Bharathwaj VV, Dhamodhar D, Sathiyapriya S. Effect of Asfotase Alfa in the Treatment of Hypophosphatasia- A Systematic Review. J Pharm Bioallied Sci. 2023 Jul;15(Suppl 1):S101-S104. doi: 10.4103/jpbs.jpbs_662_22. Epub 2023 Jul 5. PMID: 37654393; PMCID: PMC10466581.
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