Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio A, is a rare, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS), which catalyzes a step in the catabolism of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). It leads to accumulation of the KS and C6S, mainly in bone and cornea, causing a systemic skeletal chondrodysplasia. MPS IVA has a variable age of onset and variable rate of progression. Common presenting features include elevation of urinary and blood KS, marked short stature, hypoplasia of the odontoid process, pectus carinatum, kyphoscoliosis, genu valgum, laxity of joints and corneal clouding; however there is no central nervous system impairment. Generally, MPS IVA patients with a severe form do not survive beyond the third decade of life whereas those patients with an attenuated form may survive over 70 years. There has been no effective therapy for MPS IVA, and care has been palliative. Enzyme replacement therapy (ERT) and hematopoietic stem cell therapy (HSCT) have emerged as a treatment for mucopolysaccharidoses disorders, including Morquio A disease. This review provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS IVA and describes potential perspectives of ERT and HSCT. The issue of treating very young patients is also discussed.

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues;however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are

The purpose of this study was to evaluate the need for the use of a foot abduction orthosis (FAO) in the treatment of idiopathic clubfeet using the Ponseti technique. Forty-four idiopathic clubfeet were treated with casting using the Ponseti method followed by FAO application. Compliance was defined as full-time FAO use for 3 months and part-time use subsequently. Noncompliance was failure to fulfill the criteria during the first 9 months after casting. Feet were rated according to the Dimeglio and Pirani scoring systems at initial presentation, at the time of FAO application, and at 6 to 9 months of follow-up. At the time of application, no significant differences in scores were found between the groups. At follow-up, the compliant group's scores were significantly (P < 0.01) better than those of the noncompliant group. From the time of application to follow-up, for the compliant group, the Dimeglio scores improved significantly (P = 0.005). For the noncompliant group, the Dimeglio scores deteriorated significantly (P = 0.001). The feet of patients compliant with FAO use remained better corrected than the feet of those patients who were not compliant. Proper use of FAO is essential for successful application of the Ponseti technique.

PurposeDifferent treatment modalities have been utilized to treat unicameral bone cyst (UBC), but evidence has not been fully described to support one treatment over another and the optimal treatment is controversial. The aim of this quantitative systematic review was to assess the effectiveness of different UBC treatment modalities.MethodsWe utilized Pubmed to isolate retrospective studies on patients with UBC who received any kind of treatment. The included studies needed to have a minimum sample size of 15 patients, and have provided data on radiographic healing outcome.ResultsSixty-two articles were selected for the meta-analysis from a total of 463 articles. The cumulative sample size was 3,211 patients with 3,217 UBC, and male to female ratio was 2.2:1. The summary or pool estimate of methylprednisolone acetate (MPA) injection resulted in a healing rate of (77.4 %) that was comparable to bone marrow injection (77.9 %). A higher healing rate was observed with MPA injection when inner wall disruption was performed. The pool estimate of bone marrow with demineralized bone matrix injection was high (98.7 %). UBC healing rate after surgical curettage was comparable whether autograft or allograft was utilized (90 %). UBC treatment with flexible intramedullary nails without curettage provided almost 100% healing rate, while continuous decompression with cannulated screws provided 89 % healing rate. Conservative treatment indicated a healing rate of 64.2, 95 % CI (26.7–101.8).ConclusionsActive treatment for UBC provided variable healing rates and the outcomes were favorable relative to conservative treatment. Due to the heterogeneity of the studies and reporting bias, the interpretation of these findings should be handled with caution.

Patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) have accumulation of the glycosaminoglycans, keratan sulfate, and chondroitin-6-sulfate, in bone and cartilage, causing systemic spondyloepiphyseal dysplasia. Features include lumbar gibbus, pectus carinatum, faring of the rib cage, marked short stature, cervical instability and stenosis, kyphoscoliosis, genu valgum, and laxity of joints. Generally, MPS IVA patients are wheelchair-bound as teenagers and do not survive beyond the second or third decade of life as a result of severe bone dysplasia, causing restrictive lung disease and airway narrowing, increasing potential for pneumonia and apnea; stenosis and instability of the upper cervical region; high risk during anesthesia administration due to narrowed airway as well as thoracoabdominal dysfunction; and surgical complications. Patients often need multiple surgical procedures, including cervical decompression and fusion, hip reconstruction and replacement, and femoral or tibial osteotomy, throughout their lifetime. Current measures to intervene in disease progression are largely palliative, and improved therapies are urgently needed. A clinical trial for enzyme replacement therapy (ERT) and an investigational trial for hematopoietic stem cell transplantation (HSCT) are underway. Whether sufficient enzyme will be delivered effectively to bone, especially cartilage (avascular region) to prevent the devastating skeletal dysplasias remains unclear. This review provides an overview of historical aspects of studies on MPS IVA, including clinical manifestations and pathogenesis of MPS IVA, orthopedic surgical interventions, and anesthetic care. It also describes perspectives on potential ERT, HSCT, and gene therapy.

Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.

BackgroundMusculoskeletal involvement in Morquio A syndrome (mucopolysaccharidosis IVA; MPS IVA) contributes significantly to morbidity and mortality. While the spinal manifestations of the disorder have received considerable attention in the literature, there have been few reported studies to date to guide the management of the orthopedic problems associated with the lower and upper extremities.PurposeThe objective was to develop recommendations for the management of the extremities in patients with Morquio A syndrome.MethodsA group of specialists in orthopedics, pediatrics and genetics with experience in the management of Morquio A patients convened to review and discuss current clinical practices and to develop preliminary recommendations. Evidence from the literature was retrieved. Recommendations were further refined until consensus was reached.Results and conclusionsThis present article provides a detailed review and discussion of the lower and upper extremity deformities in Morquio A syndrome and presents recommendations for the assessment and treatment of these complications. Key issues, including the importance of early diagnosis and the implications of medical therapy, are also addressed. The recommendations herein represent an attempt to develop a uniform and practical approach to managing patients with Morquio A syndrome and improving their outcomes.

Unplanned surgery for soft tissue sarcomas of the foot and ankle often results in the need for more aggressive surgery and/or adjuvant radiotherapy and may impact oncologic outcomes, but does not necessarily portend worse functional outcomes. Multimodal therapy and judicious use of soft tissue flap reconstruction allows limb salvage in most patients with favorable outcomes.