Mucopolysaccharidosis type IVA (MPS IVA, or Morquio syndrome type A) is an inherited metabolic lysosomal disease caused by the deficiency of the N-acetylglucosamine-6-sulfate sulfatase enzyme. The deficiency of this enzyme accumulates the specific glycosaminoglycans (GAG), keratan sulfate, and chondroitin-6-sulfate mainly in bone, cartilage, and its extracellular matrix. GAG accumulation in these lesions leads to unique skeletal dysplasia in MPS IVA patients. Clinical, radiographic, and biochemical tests are needed to complete the diagnosis of MPS IVA since some clinical characteristics in MPS IVA are overlapped with other disorders. Early and accurate diagnosis is vital to optimizing patient management, which provides a better quality of life and prolonged life-time in MPS IVA patients. Currently, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available for patients with MPS IVA. However, ERT and HSCT do not have enough impact on bone and cartilage lesions in patients with MPS IVA. Penetrating the deficient enzyme into an avascular lesion remains an unmet challenge, and several innovative therapies are under development in a preclinical study. In this review article, we comprehensively describe the current diagnosis, treatment, and management for MPS IVA. We also illustrate developing future therapies focused on the improvement of skeletal dysplasia in MPS IVA.

It is known that empathic communication is important for physicians to achieve higher patient satisfaction and health outcomes. Emotional intelligence (EI), empathy and personality in medical students predict students’ individual disposition and their emotional and empathic perceptions. This study aimed to investigate: 1) The association between empathy, EI and personality, and 2) Gender differences in the association between empathy, EI and personality. Participants were 357 1st year medical students from 2008 to 2011 at one medical school in Japan. Students completed self-report questionnaires comprising three validated instruments measuring EI: Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF), empathy: Jefferson Scale of Physician Empathy- student version (JSPE) and personality: NEO-Five-Factor Inventory (NEO-FFI), which explores 5 dimensions of personality Neuroticism (N), Extraversion (E), Openness to experience (O), Agreeableness (A), and Conscientiousness (C). Pearson Correlations showed weak association between TEIQue-SF and JSPE. TEIQue-SF and NEO-FFI showed positive correlation for E and C, and strong negative correlation for N and weak positive correlation for A and O. Weak positive correlation between JSPE and the NEO-FFI were observed for E and A. Although effect sizes were small, N, A and empathy were significantly higher in females (unpaired t-test). However, hierarchical multiple-regression analysis when controlling for gender and personality showed no association between EI, empathy and gender. A, TEIQue-SF and N were found to make small contributions in respect of predictions for JSPE. Personality contributed significantly to the prediction of TEIQue-SF. N had the largest independent negative contribution (β = − 0,38). In our study population of 1st year medical students, females had significantly higher N, A and empathy scores than males. Medical students’ N score was strongly negatively associated with EI. Empathy was weakly associated with EI and A. However, when controlling gender and personality in regression analysis, gender did not affect EI and empathy, rather personality is the most important factor. Our findings indicate that N is a major factor that negatively affects EI. It is important to mitigate N using thoughtful training, taking into account students’ personalities, to reduce N. In future studies, we will assess how communication trainings for students might enhance EI.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high-throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs.

Patients with Hunter syndrome (mucopolysaccharidosis II) present with skeletal dysplasia including short stature as well as CNS and visceral organ involvement. A previous study on Hunter syndrome indicated an impact on brain and heart involvement after hematopoietic stem cell therapy (HSCT) at an early stage but little impact after enzyme replacement therapy (ERT) (Tanaka et al. 2012). Meanwhile, impact on growth in patients with Hunter syndrome treated with ERT and HSCT has not been compared until now. We recently developed baseline growth charts for untreated patients with Hunter syndrome to evaluate the natural history of growth of these patients compared to unaffected controls (Patel et al., 2014).

Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia.