ESPE Abstracts (2019) 92 P2-51

Perinatal form Hypophosphatasia Caused by a Novel Large Duplication of ALPL Gene and two year follow-up under Enzyme Replacement Therapy; A case report

Bulent Hacihamdioglu1, Gamze Ozgurhan2, Catarina Pereira3, Emre Tepeli2, Gulsen Acar2, Serdar Comert2


1Istinye University, Istanbul, Turkey. 2University of Health Sciences, Istanbul, Turkey. 3Centogene AG, Rostock, Germany


Hypophosphatasia is a rare disease caused by mutations in the gene encoding tissue- nonspecific isoenzyme of alkaline phosphatase. Duplications of the ALPL gene account for fewer than 1% of the mutations causing HPP. It has been shown that asfotase alfa treatment mineralizes the skeleton and improves respiratory function and survival in severe forms of hypophosphatasia.

The newborn was evaluated for respiratory failure and generalized hypotonia after birth. Diagnosis of HPP was based on low-serum ALP activity, high levels of substrates of tissue-nonspecific isoenzyme of alkaline phosphatase and radiologic findings. On day 21 after birth, enzyme replacement therapy using asfotase alfa (2 mg/kg three times per week, subcutaneous injection) was started. We were able to discharge our patient when he was 7 months old. His respiratory support was gradually reduced and skeletal mineralization improved during treatment. We increased the dose when he 13 month-old due to incomplete resolution of radiological rickets findings. He has been no need any respiratuary support after 18 month old. He was operated for craniosynostosis at 23 month old. No mutation was detected in the ALPL gene by all exon sequencing, and additional analysis was done by quantitative polymerase chain reaction. As a result, a novel homozygote duplication encompassing exons 2 to 6 was detected.

Early diagnosis and rapid intervention with enzyme replacement therapy is life-saving in the severe form of hypophosphatasia. Craniosynostosis can occur these patients although early enzyme replacement therapy. Quantitative polymerase chain reaction can detect duplications if a mutation cannot be detected by sequence analysis in patients with hypophosphatasia.

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