ESPE Abstracts

Hypophosphatasia (HPP) is a rare genetic disease caused by mutations with loss of function in the ALPL gene, which encodes for non-specific tissue alkaline phosphatase (TNSALP). We report a case of infantile hypophosphatasia. Due to positive family history for hypophosphatasia, a chorionic villus sampling was made, with evidence in composed heterozygous of variants c.407G>A and c.1489T>C in the ALPL gene. At birth the patient did not have clinical complications, however the blood concentrations of alkaline phosphatase and vitamin B6 confirmed the diagnosis. On the third day of life, treatment with asfotase alfa has been started at a dose of 2 mg/kg three times a week subcutaneously. Treatment has always been well tolerated. Subsequent blood tests showed a progressive increase in alkaline phosphatase activity and a normalization of vitamin B6 concentrations, as expected. Plasmatic concentrations of calcium, phosphorus and parathyroid hormone have always remained within the normal limits. Starting from the third month of age, a progressive worsening of the cranial conformation has been noted with the appearance of marked asymmetry of forehead (left > right) and apparent hypoplasia of the left eyebrow arch. The anterior fontanel was, however, of normal size and conformation and the neuromotor development progressed regularly. At 6 months of life, Head CT with 3D reconstruction was carried out, with evidence of craniosynostosis of the right coronal suture. The patient was then referred for neurosurgical evaluation and is currently awaiting corrective surgery. As reported in literature, about 2/3 of patients with childhood-onset hypophosphatasia present craniosynostosis as a complication; therefore, it is important to monitor the possible occurrence of this condition and eventually direct patients to a correct multidisciplinary diagnostic and therapeutic process. It is also important that the follow up continues for a long time after the surgical correction because due to the underlying metabolic defect, recurrences are more frequent than in patients not affected. To date, further studies are needed to determine whether the introduction of enzyme replacement therapy can change the incidence and presentation of this complication. However, it is possible to hypothesize that treatment with asfotase alfa, will improve the quality of bones, contributing to the success of surgical correction, while reducing the risks associated with the pathology.