Management of Craniosynostosis in Lethal Perinatal Hypophosphatasia.

Although perinatal lethal hypophosphatasia (HPP) was once a disease with a universally poor prognosis, it has now become a rare but treatable condition with the advent of enzyme replacement therapy with asfotase alfa. As a result, a greater population of patients with perinatal HPP are presenting with abnormal head shape and craniosynostosis. The authors present here 3 cases of perinatal lethal HPP, 1 treated with traditional open cranial vault remodeling and 2 treated utilizing distraction osteogenesis techniques. All patients demonstrated outcomes comparable to those previously reported with traditional observation or open cranial vault repair. Thorough consideration and discussion between the surgical team and patient's family is needed to determine a treatment plan that best addresses the goals of patient and family in light of recent advances in medical treatment in this rare patient population in which surgical interventions were previously nearly impossible. This article further supports the safety and efficacy of surgical intervention and explores the utility of distraction osteogenesis to address craniosynostosis in this patient population.

Hypophosphatasia and cleidocranial dysplasia-a case report and review of the literature: the role of the neurosurgeon.

Hypophosphatasia (HPT) and cleidocranial dysplasia (CCD) are rare genetic disorders characterized by both defective ossification and bone mineralization. Patients usually present with craniosynostosis and cranial defects which in many cases require surgical repair. There is only 1 reported case of combined HPT and CCD in the literature. Our reported case involves a 3.5-year-old girl with concomitant homozygous CCD and heterozygous HPT. The child had an extended cranial defect since birth which improved with the administration of Strensiq and was followed until preschool age. Bone defects were relatively minor on revaluation. Due to the limited final defect, we decided not to intervene. In HPT-CCD patients, bone defects are overestimated due to osteomalacia, and thus, management strategy should be less aggressive. They should undergo surgical repair with cranioplasty with the use of cement and/or titanium meshes in case of extended final defects.

Enzyme replacement therapy for congenital hypophosphatasia allows for surgical treatment of related complex craniosynostosis: a case series.

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.

Cell therapy for disorders of bone.

Bone marrow transplantation (BMT) has changed the course of treatment for an array of diseases, including disorders of bone. Hematopoietic stem cells (HSC) within the marrow are known to be the precursors of osteoclastic bone cells, and trials of BMT in osteopetrosis, a disorder characterized by a deficiency of osteoclasts, have resulted in significant clinical improvement in patients. The origin of the other major bone cell, the osteoblast, remains uncertain, although studies have identified osteoprogenitor cells within the marrow, leading to further investigation of both mesenchymal stromal cells (MSC) and HSC as candidates for this role. A better understanding of the source of osteoblasts and normal bone metabolism is crucial to efforts to develop effective cell therapy for bone disorders characterized by deficient or abnormal osteoblast function. This review focuses on systemic and local cell therapy in the treatment of several genetic bone disorders and osteoporosis, an acquired disorder caused by abnormal bone metabolism, with the intent of presenting both the progress and challenges associated with this emerging form of therapy. Although the risks of systemic transplantation must be carefully considered, cell therapy for disorders of bone carries the potential for long-term and potentially curative benefits, justifying further intensive research on this important treatment option.

Intramedullary nailing for adult hypophosphatasia: a case report.

Hypophosphatasia is a rare genetic metabolic disorder characterised by defective bone mineralisation secondary to serum and bone alkaline phosphatase deficiency. We report a 46-year-old woman who underwent multiple intramedullary nailings for fractures and deformities of 6 long bones over 13 years.