{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T09:09:09Z","timestamp":1779527349351,"version":"3.53.1"},"reference-count":34,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FOC"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>Hypophosphatasia (HPP) is a rare inherited disorder of bone metabolism that results in the loss of function of the gene coding for tissue-nonspecific alkaline phosphatase (TNSALP). Patients with HPP have defective bone mineralization as well as craniosynostosis that can be seen in the infantile and childhood forms of this disease. Traditionally, HPP has had a poor prognosis, with few children surviving to exhibit the phenotype of clinical craniosynostosis that requires surgical intervention. Here, the authors report on new advancements in enzyme replacement therapy (ERT) for children affected by HPP, allowing these patients to survive and undergo surgery to address complex craniosynostosis. The authors discuss their case series of 4 HPP patients treated at their institution with ERT who have undergone successful surgical intervention for craniosynostosis. These children had no complications related to their surgeries and exhibited decreased neurological symptoms following cranial vault remodeling. This study reveals that ERT administered either pre- or post- operatively paired with cranial vault remodeling strategies can yield improved neurological outcomes in children affected by HPP.<\/jats:p>","DOI":"10.3171\/2015.2.focus14847","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T03:36:59Z","timestamp":1430451419000},"page":"E10","source":"Crossref","is-referenced-by-count":16,"title":["Enzyme replacement therapy for congenital hypophosphatasia allows for surgical treatment of related complex craniosynostosis: a case series"],"prefix":"10.3171","volume":"38","author":[{"given":"Libby","family":"Kosnik-Infinger","sequence":"first","affiliation":[{"name":"Divisions of Pediatric Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Gendron","sequence":"additional","affiliation":[{"name":"Plastic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Plastic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Pan","sequence":"additional","affiliation":[{"name":"Plastic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"van Aalst","sequence":"additional","affiliation":[{"name":"Plastic Surgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Divisions of Pediatric Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-focus14847","series-title":"Bone","first-page":"1655","article-title":"Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene","volume":"40","author":"Baumgartner-Sigl","year":"2007"},{"key":"b2-focus14847","series-title":"J Clin Endocrinol Metab","first-page":"2923","article-title":"Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteo- blasts","volume":"92","author":"Cahill","year":"2007"},{"key":"b3-focus14847","series-title":"J Neurosurg","first-page":"575","article-title":"Chronic tonsillar herniation in Crouzon\u2019s and Apert\u2019s syndromes: the role of premature synostosis of the lambdoid suture","volume":"83","author":"Cinalli","year":"1995"},{"key":"b4-focus14847","series-title":"Childs Nerv Syst","first-page":"217","article-title":"Neurosurgical aspects of childhood hypophosphatasia","volume":"25","author":"Collmann","year":"2009"},{"key":"b5-focus14847","series-title":"Childs Nerv Syst","first-page":"902","article-title":"Hydrocephalus in craniosynostosis: a review","volume":"21","author":"Collmann","year":"2005"},{"key":"b6-focus14847","series-title":"Medicine (Baltimore)","first-page":"12","article-title":"Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms","volume":"63","author":"Fallon","year":"1984"},{"key":"b7-focus14847","series-title":"Nature","first-page":"901","article-title":"Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeosta- sis","volume":"212","author":"Fleisch","year":"1966"},{"key":"b8-focus14847","series-title":"Pediatr Neurosurg","first-page":"185","article-title":"Brainstem gliomas in children. A Children\u2019s Cancer Group review of 119 cases","volume":"24","author":"Kaplan","year":"1996"},{"key":"b9-focus14847","series-title":"J Inherit Metab Dis","first-page":"35","article-title":"Glu274Lys\/Gly309Arg mutation of the tissue- nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions","volume":"25","author":"Litmanovitz","year":"2002"},{"key":"b10-focus14847","series-title":"J Can Assoc Radiol","first-page":"16","article-title":"Hypophosphatasia","volume":"23","author":"Macpherson","year":"1972"},{"key":"b11-focus14847","series-title":"Actual osteol","first-page":"164","article-title":"Hypophosphatasia - pathophysiology and treatment","volume":"8","author":"Mill\u00e1n","year":"2012"},{"key":"b12-focus14847","series-title":"J Craniofac Surg","first-page":"417","article-title":"Bilambdoid and posterior sagittal synostosis: the Mercedes Benz syndrome","volume":"9","author":"Moore","year":"1998"},{"key":"b13-focus14847","series-title":"Orphanet J Rare Dis","first-page":"40","article-title":"Hypophosphatasia","volume":"2","author":"Mornet","year":"2007"},{"key":"b14-focus14847","series-title":"GeneReviews","article-title":"Hypophosphatasia","author":"Mornet","year":"2011"},{"key":"b15-focus14847","series-title":"J Bone Miner Res","first-page":"2389","article-title":"Hypophosphatasia: nonlethal disease despite skeletal presentation in utero (17 new cases and literature review)","volume":"26","author":"Wenkert","year":"2011"},{"key":"b16-focus14847","series-title":"N Engl J Med","first-page":"904","article-title":"Enzyme-replacement therapy in life- threatening hypophosphatasia","volume":"366","author":"Whyte","year":"2012"},{"key":"b17-focus14847","series-title":"J Bone Miner Res","first-page":"624","article-title":"Marrow cell transplantation for infantile hypophosphatasia","volume":"18","author":"Whyte","year":"2003"},{"key":"b1-focus14847","series-title":"Bone","first-page":"1655","article-title":"Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene","volume":"40","author":"Baumgartner-Sigl","year":"2007"},{"key":"b2-focus14847","series-title":"J Clin Endocrinol Metab","first-page":"2923","article-title":"Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteo- blasts","volume":"92","author":"Cahill","year":"2007"},{"key":"b3-focus14847","series-title":"J Neurosurg","first-page":"575","article-title":"Chronic tonsillar herniation in Crouzon\u2019s and Apert\u2019s syndromes: the role of premature synostosis of the lambdoid suture","volume":"83","author":"Cinalli","year":"1995"},{"key":"b4-focus14847","series-title":"Childs Nerv Syst","first-page":"217","article-title":"Neurosurgical aspects of childhood hypophosphatasia","volume":"25","author":"Collmann","year":"2009"},{"key":"b5-focus14847","series-title":"Childs Nerv Syst","first-page":"902","article-title":"Hydrocephalus in craniosynostosis: a review","volume":"21","author":"Collmann","year":"2005"},{"key":"b6-focus14847","series-title":"Medicine (Baltimore)","first-page":"12","article-title":"Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms","volume":"63","author":"Fallon","year":"1984"},{"key":"b7-focus14847","series-title":"Nature","first-page":"901","article-title":"Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeosta- sis","volume":"212","author":"Fleisch","year":"1966"},{"key":"b8-focus14847","series-title":"Pediatr Neurosurg","first-page":"185","article-title":"Brainstem gliomas in children. 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