Purpose or Case Report: To review the imaging appearance of the skull in hypophasphatasia (HPP). This pictorial review includes the serial imaging appearances, commencing from diagnosis, and throughout treatment with enzyme replacement therapy (ERT). The development of craniosynostosis is shown, as is the post surgical appearance following total cranial vault remodelling.
Methods & Materials: Background:
Hypophosphatasia (HPP) is a rare disorder of bone metabolism that results in defective bone mineralisation. The underlying mutations affect the gene for tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Perinatal and infantile forms of HPP traditionally carried poor prognosis, with respiratory compromise carrying significant morbidity. Craniosynostosis is a common feature of these forms of HPP. A novel enzyme replacement therapy (ERT), asfotase alfa, (Alexion Pharmaceuticals, New Haven) results in skeletal remineralisation and improved respiratory and motor function. Craniosynostosis remains a common feature post ERT, however the skeletal healing allows for surgical options such as total cranial vault remodelling to allow cranial expansion and reduce intracranial complications.
Results: The serial imaging appearance of the skull of two children with infantile HPP are presented. The first patient was diagnosed at birth, and has a severe manifestation, with near complete absence of cranial mineralisation on initial radiographs. Treatment with ERT over an 18 month period was monitored with serial images, including ultrasound, radiographs and CT. Craniosynostosis of the sagittal suture with dolicocephaly is depicted.

A second patient had an antenatally detected skeletal abnormality, with the definitive diagnosis of HPP made in the neonatal period. The skeletal demineralisation was less striking in this patient. During the course of ERT, bilateral coronal suture craniosynostosis emerged, and was treated with total cranial vault remodelling.
Conclusions: Infantile HPP treated with ERT will become more common, given the recent FDA approval for asfotase alfa. Despite treatment, craniosynostosis remains a feature of the disease. In cases where initial cranial mineralisation/ossification is nearly absent, this may seem paradoxical; thus it is important to remain aware of this feature of HPP, and suggest further imaging with CT if craniosynostosis is suspected. With improved mineralisation of the bones post ERT, surgical options to treat craniosynostosis in patients with HPP are feasible.