Evaluation of cardiac findings in mucopolysaccharidosis.

PURPOSE: Mucopolysaccharidoses (MPS) are a group of rare genetic diseases and heart involvement is one of the important conflicts in most types, which may cause serious complications. We used M-Mode and two-dimensional speckle tracking echocardiography (2D-STE) to explore cardiovascular involvements in MPS patients. METHOD: The present cross-sectional study investigated the frequency of cardiac involvements in MPS patients. Included participants were MPS types I, II, III, IV, and VI who underwent specialized echocardiography exams to assess valvular function, systolic and diastolic function, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). RESULTS: 35 patients were enrolled in this study. The total mean age of patients was 9.58 ± 5.11 years and 71.4% were male. Type IV (40%) and type III (31.4%) were the most frequent MPS. Although LVEF did not differ notably among MPS types, GLS was significantly different (p = 0.029). Mitral regurgitation was observed remarkably more in MPS type III (p = 0.001) while mitral stenosis was more common in type III (p = 0.007). There was a significant association between LVEF and GLS (ß= -0.662; p = 0.025) and between LVEF and MPS type (ß = 1.82; p = 0.025) when adjusted for GLS. CONCLUSION: Cardiac complications are very common and are one of the most important causes of death in MPS patients. 2D-STE seems to be superior to M-Mode for detection of early and subclinical cardiac dysfunction in MPS patients.

Capsular and retinaculum thickening in type II mucopolysaccharidosis: a novel MRI finding.

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage diseases caused by a deficiency of glycosaminoglycan (GAG) catalytic enzymes, resulting in an accumulation of unprocessed or partly degraded GAGs in different tissues, including bones and joints. Notably, skeletal and joint abnormalities may be the first complaint that prompts patients to seek medical attention, especially in the milder forms of the disease. To our knowledge, there are no prior imaging reports that have documented capsuloligamentous thickening in patients with MPS on MRI. In this study, we present four cases of patients with clinically and genetically confirmed diagnosis of type II MPS, encompassing seven MRI examination of different joints, including cervical spine, hip, wrist, knee, and shoulder. All of the patients were male, aged between 14 and 35 years, and exhibited varying degrees of joint stiffness in the clinical examination and carpal tunnel syndrome in cases of the wrist joint was affected. None of the patients had a history of surgical procedures on the affected joint, other metabolic or deposit diseases, or sports activity practice. The MRI revealed significant capsuloligamentous and retinaculum thickening, up to eight times greater than the normal capsular thickness reported in the literature.

Tissue doppler echocardiographic evaluation of cardiac functions in children with mucopolysaccharidosis type III disease.

Background: Mucopolysaccharidosis type III (MPS III) is an extremely rare group of diseases among all MPS types. In recent years, there are studies about the presence and importance of cardiac involvement in MPS III patients as in other types of MPS. Aim: The aim of our study is to evaluate the cardiac functions of MPS III patients in pediatric age by using the M-mode, 2D, and Tissue Doppler echocardiographic measurements. Methods: The study was conducted prospectively between September and December 2020. Fifteen MPS III patients and 15 healthy volunteers were included in the study. Results: The mean Tei indexes of all three regions including left ventricle (LV), right ventricle (RV), and interventricular septum (IVS) were higher in MPS III patients compared to the control group (0.43/0.36 for LV and 0.44/0.37 for RV and 0.41/0.35), respectively. Diastolic function parameters of MPS III Patients were worse than the control group. In MPS III patients, eight (53.3%) patients had valvular dysfunction, three (20%) patients asymmetric septal hypertrophy and four (26.7%) patients LV concentric remodeling pattern. We detected an increase of z score above +2 in aortic valve annulus, sinuses of Valsalva, IVS diastole diameter and also in the LV posterior wall diastole diameter measurements in some MPS III patients. Conclusion: We conclude that cardiac monitoring of MPS III patients is very important in terms of early detection and treatment of cardiac problems that may arise. Cardiac evaluation of larger series of MPS III patients are needed to make a better decision.

Radiographic Findings of Mucopolysaccharidosis and Comparison with Bone Mineral Density: A Study from Southeastern Turkey.

INTRODUCTION: The first aim of this study is to define the severity of radiologic features according to mucopolysaccharidosis (MPS) type. The second aim is to compare spine radiographs with dual-energy X-ray absorptiometry (DXA) scores. METHODOLOGY: A total of 64 MPS children were enrolled between January 2017 and March 2021. Patients with a history of surgery, fracture or improper radiographs were excluded. Finally, 48 cases (20 MPS VI, 12 MPS IVA, 7 MPS IIIA, 4 MPS IIIB, 3 MPS II, 2 MPS I) were yielded. Among them, 38 had DXA performed in the same week with radiographs. Demographic and radiographic features and the hip acetabular index were noted. T12-L5 vertebral body heights were measured from lateral spine radiographs and divided by patient height. DXA measurements, bone mineral density and Z-scores were also recorded. RESULTS: Spine and hip findings were most frequently seen in MPS VI and IVA. Oar-shaped ribs were more common in MPS VI, whereas anteromedial beaking of vertebra was predominantly seen in MPS IVA. Femoral head dysplasia is most common in MPS IVA, VI and I. The highest mean acetabular was observed in MPS I. The mean Z-score of L1-L4 vertebrae was low for MPS I (-3.8), IVA (-3.79) and VI (-3.73), but normal for MPS II (0.6) and IIIA (0.23). Correlation between the Z-score and vertebral index was highest in the L1 vertebral body. CONCLUSION: Interpreting the characteristic radiographic features of different MPS types is important. In addition to dysostosis multiplex, quantitative measurements from radiographs may be beneficial in evaluating disease progression.

Mandibular condyle morphology among patients with mucopolysaccharidosis: An observational study of panoramic radiographs.

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of rare metabolic diseases characterized by a wide spectrum of symptoms including progressive condylar resorption. AIM: The aim of this study was to quantify the severity of condylar involvement in MPS I individuals in comparison with a group of non-MPS individuals and to describe how condylar changes may vary among the different types of MPS. DESIGN: Fifty panoramic radiographs of MPS patients (13.4 ± 6.2 years) with MPS I (n = 14), MPS II (n = 2), MPS IV (n = 8) and MPS VI (n = 2) were compared with forty panoramic radiographs of non-MPS individuals. The severity of condylar resorption was evaluated using a qualitative score (grades 0-3) and using the ratio of condylar height to ramus height (CH: RH). RESULTS: All MPS I and VI individuals showed pronounced bilateral degenerative condylar resorption. In contrast, individuals with MPS II and IV exhibited heterogeneous findings. The quantification of condylar height to ramus height revealed that CH: RH was significantly decreased in MPS I as compared to that of non-MPS individuals (P < .001). In contrast, the CH: RH ratios of MPS II and IV showed great variability. CONCLUSION: Mucopolysaccharidoses subtypes differ with regard to the severity of condylar resorption.

Features and behavior of valvular abnormalities in adolescent and adult patients in mucopolysaccharidosis: an echocardiographic study.

Mucopolysaccharidoses, a rare inherited disorder of lysosomal storage, account for less than 0.1% of all genetic diseases.  The penetrance is highly variable and clinically it varies from severe fetal-neonatal forms to attenuated diseases diagnosed in adult individuals. The majority of the patients have been reported to show cardiac abnormalities since pediatric age, however, there is a minority of patients with attenuated disease diagnosed in the adolescent and adult age. The haematopoietic stem cell transplantation and enzyme replacement therapy are the current therapies for these disorders. Thanks to these treatments, Mucopolysaccharidoses patients live longer than in the past. Even though enzyme replacement therapy has been demonstrated to reduce left ventricular mass in patients with cardiomyopathy, the efficacy on valve abnormalities has not been clearly demonstrate yet. Furthermore, thanks to the current therapy, to better understanding and to the advent on new technologies, an increasing number of adolescent and adult patients diagnosed with MPS are followed up in the adult echocardiographic laboratory. Indeed, a systematic descriptive study describing the echocardiographic features of valvular involvement and their evolution in adolescent and adult patients lacks of medical literature and this was the aim of our investigation. Our results showed that all the valves are affected, mainly the mitral valve with a higher prevalence compared to the pediatric age.  The echocardiographic features of MPS differs from other valvular disease of adolescent and adult age, and knowing them can avoid misdiagnosis. Our observations also suggest that the progression of cardiac involvement slows after the initiation of the therapy in our group of age. Further studies on larger population are required to confirm our results.

Dental and maxillomandibular incidental findings in panoramic radiography among individuals with mucopolysaccharidosis: a cross-sectional study.

Mucopolysaccharidosis (MPS) is a group of rare and inherited metabolic disorders caused by the accumulation of macromolecule glycosaminoglycans inside lysosomes. Affected individuals may have dental and craniofacial tissue alterations, facilitating the development of several oral diseases. OBJECTIVES: To assess, with panoramic radiographic images, the frequency of dental and maxillomandibular incidental findings among MPS individuals and compare them with non-MPS individuals. METHODOLOGY: A cross-sectional study evaluating a sample of 14 MPS individuals and 28 non-MPS individuals aged from 5 to 26 years was carried out. They were matched for sex and age on a 2:1 proportion. Panoramic radiographs were assessed for the presence/absence of the following dental and maxillomandibular alterations: dental anomalies of number (hypodontia/dental agenesis, supernumerary teeth); anomalies of form (microdontia, macrodontia, conoid teeth, taurodontism, and root dilaceration); anomalies of position (impacted tooth, inverted tooth, tooth migration, partially bony teeth, complete bony teeth); periapical alterations (furcation lesion, circumscribed bone rarefaction); other alterations (radiolucent bone lesions, radiopaque bone lesions, radiopacity in the maxillary sinus, condylar hypoplasia). Differences between groups were tested by the Fisher's exact test and chi-square test (p<0.05). RESULTS: For intrarater agreement, Kappa values were 0.76 to 0.85. The presence of supernumerary teeth (p=0.003); conoid teeth (p=0.009); taurodontism (p<0.001); impacted teeth (p<0.001); partial bony teeth (p=0.040); complete bony teeth (p=0.013); and root dilaceration (p=0.047) were statistically more frequent in MPS individuals compared to non-MPS individuals. Bone rarefaction/furcation lesions (p=0.032), condylar hypoplasia (p<0.001), radiolucent bone lesions (p=0.001), and dentigerous cysts (p=0.002) were also more frequent in MPS individuals. CONCLUSION: The presence of specific oral manifestations is more common in MPS individuals than non-MPS individuals.

Hip pathologies in mucopolysaccharidosis type III.

BACKGROUND: Mucopolysaccharidosis type III (MPS III) comprises a group of rare lysosomal storage diseases. Although musculoskeletal symptoms are less pronounced than in other MPS subtypes, pathologies of hip and spine have been reported in MPS III patients. The purpose of this study was to describe hip pathologies and influencing parameters in MPS III patients. METHODS: A retrospective chart review was performed for 101 MPS III patients. Thirty-two patients met the inclusion criteria of enzymatically or genetically confirmed diagnosis and anteroposterior radiograph of the hips. Modified Ficat classification, Wiberg's center-edge angle, and Reimer's migration percentage were measured. RESULTS: The mean age at data assessment was 11.0 years (SD 5.7). Osteonecrosis of the femoral head was observed in 17/32 patients. No statistically significant association was found between these changes and age, sex, or MPS III subtype. Patients with a severe phenotype showed significantly higher rates of osteonecrosis (14/17) than patients with an intermediate phenotype. Hip dysplasia was present in 9/32 patients and was significantly associated with osteonecrosis of the femoral head (p = 0.04). CONCLUSIONS: The present study demonstrates a high rate of hip pathologies in MPS III patients. Hip dysplasia and severe phenotype were significantly correlated with osteonecrosis of the femoral head. Therefore, radiographs of the hips are highly recommended in baseline and follow-up assessments of MPS III patients. TRIAL REGISTRATION: Retrospectively registered.

The point-of-care use of a facial phenotyping tool in the genetics clinic: Enhancing diagnosis and education with machine learning.

Computer-assisted pattern recognition platforms, such as Face2Gene® (F2G), can facilitate the diagnosis of children with rare genetic syndromes by comparing a patient's features to known genetic diagnoses. Our work designed, implemented, and evaluated an innovative model of care in clinical genetics in a heterogeneous and multicultural patient population that utilized this facial phenotyping software at the point-of-care. We assessed the performance of F2G by comparing the suggested diagnoses to the patient's confirmed molecular diagnosis. Providers' overall experiences with the technology and trainees' educational experiences were assessed with questionnaires. We achieved an overall diagnostic yield of 57%. This increased to 82% when cases diagnosed with syndromes not recognized by F2G were removed. The mean rank of a confirmed diagnosis in the top 10 was 2.3 (CI 1.5-3.2) and the mean gestalt score 37.6%. The most commonly suggested diagnoses were Noonan syndrome, mucopolysaccharidosis, and 22q11.2 deletion syndrome. Our qualitative assessment revealed that clinicians and trainees saw value using the tool in practice. Overall, this work helped to implement an innovative patient care delivery model in clinical genetics that utilizes a facial phenotyping tool at the point-of-care. Our data suggest that F2G has utility in the genetics clinic as a clinical decision support tool in diverse populations, with a majority of patients having their eventual diagnosis listed in the top 10 suggested syndromes based on a photograph alone. It shows promise for further integration into clinical care and medical education, and we advocate for its continued use, adoption and refinement along with transparent and accountable industrial partnerships.

Dental and maxillomandibular incidental findings in panoramic radiography among individuals with mucopolysaccharidosis: a cross-sectional study

Abstract Mucopolysaccharidosis (MPS) is a group of rare and inherited metabolic disorders caused by the accumulation of macromolecule glycosaminoglycans inside lysosomes. Affected individuals may have dental and craniofacial tissue alterations, facilitating the development of several oral diseases. Objectives To assess, with panoramic radiographic images, the frequency of dental and maxillomandibular incidental findings among MPS individuals and compare them with non-MPS individuals. Methodology A cross-sectional study evaluating a sample of 14 MPS individuals and 28 non-MPS individuals aged from 5 to 26 years was carried out. They were matched for sex and age on a 2:1 proportion. Panoramic radiographs were assessed for the presence/absence of the following dental and maxillomandibular alterations: dental anomalies of number (hypodontia/dental agenesis, supernumerary teeth); anomalies of form (microdontia, macrodontia, conoid teeth, taurodontism, and root dilaceration); anomalies of position (impacted tooth, inverted tooth, tooth migration, partially bony teeth, complete bony teeth); periapical alterations (furcation lesion, circumscribed bone rarefaction); other alterations (radiolucent bone lesions, radiopaque bone lesions, radiopacity in the maxillary sinus, condylar hypoplasia). Differences between groups were tested by the Fisher's exact test and chi-square test (p<0.05). Results For intrarater agreement, Kappa values were 0.76 to 0.85. The presence of supernumerary teeth (p=0.003); conoid teeth (p=0.009); taurodontism (p<0.001); impacted teeth (p<0.001); partial bony teeth (p=0.040); complete bony teeth (p=0.013); and root dilaceration (p=0.047) were statistically more frequent in MPS individuals compared to non-MPS individuals. Bone rarefaction/furcation lesions (p=0.032), condylar hypoplasia (p<0.001), radiolucent bone lesions (p=0.001), and dentigerous cysts (p=0.002) were also more frequent in MPS individuals. Conclusion The presence of specific oral manifestations is more common in MPS individuals than non-MPS individuals.

Imaging features of mucopolysaccharidoses in the head and neck.

Ear, Nose and Throat (ENT) involvement by mucopolysaccharidoses is very common, affecting over 90% of patients, and occurs early in the course of the disease. Airway narrowing secondary to glycosaminoglycan deposition results in greatly increased morbidity, mortality and risk of anesthetic complications in these patients. Macroglossia, restricted mouth opening, tracheobronchomalacia, adenotonsillar hypertrophy along with other factors such as a short, rigid and unstable cervical spine, cardiac disease and increased susceptibility to respiratory infections result in a high perioperative mortality and morbidity. Imaging is most beneficial for evaluation of the airway, in particular in patients with obstructive symptoms and prior to intubation. We review the ENT manifestations of mucopolysaccharidoses including airway involvement, otological, oral and dental complications. 3-D reconstructions of the trachea, which is routinely captured on CT imaging of the spine, can be of great value for planning intubation in this patient population.

Posterior fossa horns; a new calvarial finding of mucopolysaccharidoses with well-known cranial MRI features

Background/aim: Mucopolysaccharidoses (MPS) are a group of hereditary metabolic diseases. The aim of this study was to share the previously unreported calvarial finding of internal hypertrophy of the occipitomastoid sutures (IHOMS) together with some other well-known cranial MRI findings in this patient series. Materials and methods: A retrospective evaluation was conducted of 80 cranial MRIs of patients who had been diagnosed and followed up with MPS from 2008 to 2019 in our center. Of these patients, 11 had Hurler, 14 had Hunter, 24 had Sanfilippo, 15 had Morquio, 14 had Maroteaux­Lamy, and 2 had Sly disease. The cranial MRIs were assessed in two main groups as parenchymal intradural cranial MRI findings and extradural calvarial findings. Results: The most common parenchymal intradural cranial MRI findings were white matter signal alterations (n = 51, 63%) and perivascular space enlargements (n = 39, 48%). The most common extradural calvarial findings were J-shaped sella (n = 45, 56%) and tympanic effusion (n = 44, 55%). Although IHOMS was defined in a relatively small number of the patients (n = 12, 15%), the prevalence rate was high in MPS type I (n = 6, 54%). Conclusion: The abnormal cranial MRI findings of the MPS patients, including the newly identified IHOMS, may provide diagnostic clues to differentiate the type of the disease in radiological imaging.

Spine challenges in mucopolysaccharidosis.

PURPOSE: Mucopolysaccharidosis (MPS) are rare inherited metabolic diseases, causing lysosomal storage of mucopolysaccharides; clinical presentation involves skeletal system and particularly the spine. Anomalies include developing kyphosis at thoracolumbar junction, that can causes nervous symptoms, and dens hypoplasia with associated atlantoaxial subluxation that can cause myelopathy. We present our experience in the treatment of spine pathology in MPS. METHODS: Medical treatments of MPS seem to have little impact on spine disease: treatment of cervical instability often includes surgical decompression and stabilization, as in patient MPS1 that we present, while thoracic lumbar kyphosis is treated by bracing and, in severe cases, with surgery. Bracing is more effective in kyphosis under 40° Cobb. Our surgical cases with thoracic lumbar kyphosis over 40° Cobb, treatment include the first one ever described by only posterior approach with vertebrectomy in MPS and a case of lateral costo-transverse approach instrumented correction. RESULTS: Surgical patients had no major complications after surgery and CT scan at follow-up showed complete fusion without loss of correction, even if in a cervical case we used an adult rigid instrumentation in a four year-and-six month-old girl (11 years follow-up) and in thoracic lumbar kyphosis case treated by vertebrectomy due to diminutive anatomy we positioned interbody cage in suboptimal position. CONCLUSIONS: Bracing is a viable treatment strategy in thoracic lumbar kyphosis and can obtain good clinical results at medium terms follow-up even if kyphosis deformity remains in radiographs. Surgical treatment is effective in severe evolving cases both at cervical and thoracic lumbar level, main difficulties arose from unavailability of dedicated instrumentation in very young patient, as even smallest devices available are often too big.

In-vivo cortical thickness estimation from high-resolution T1w MRI scans in healthy and mucopolysaccharidosis affected dogs.

Cortical thickness measurement estimated from high-resolution anatomical MRI scans may serve as a marker of cortical atrophy in clinical research applications. Most of the working algorithms and pipelines are optimized for human in-vivo data analyses that offer robust and reproducible measures. As animal-models are widely utilized in many preclinical phases of clinical trials the need for an optimized automated MRI data analysis to yield reliable data is warranted. We present a processing pipeline optimized for cortical thickness estimation of canine brains in native and template spaces. Preliminary results of 5 healthy and 5 mucopolysaccharidosis (MPS) dogs demonstrate single-canine mean/median cortical thickness in range of 2.69-3.58mm in native space and 3.26-4.15mm in template space. Our MRI generated values exceed previous histological measurements (observed mean about 2mm) in limited literature reports. Randomly selected manual measures corroborated the ranges defined by estimated cortical thickness probability density functions. Geometric transformations between native and template spaces change absolute mean/median cortical thickness values, but do not change the data nature and properties since the Pearson correlation coefficients between different space estimates were 0.84 for mean values and 0.89 for median values. No significant difference in total cortical thickness between MPS and age-and gender-matched dogs was observed.

The role of imaging in the skeletal involvement of mucopolysaccharidoses.

This article discusses the role of imaging modalities including radiography, multi-detector computed tomography, magnetic resonance imaging, and ultrasound in diagnosing and monitoring skeletal abnormalities in mucopolysaccharidoses (MPS). The advantages and disadvantages of these different imaging tools will be discussed, along with their feasibility in this class of patients. As the musculoskeletal involvement is common to all MPS and is one of the main reasons for seeking medical attention, an increased awareness among paediatricians, rheumatologists, orthopaedists, radiologists, and other musculoskeletal specialists on the possible spectrum of abnormalities observed could facilitate a timely diagnosis, an appropriate severity evaluation, and better management.

Mucopolysaccharidoses: overview of neuroimaging manifestations.

The mucopolysaccharidoses are a heterogeneous group of inherited lysosomal storage disorders, characterized by the accumulation of undegraded glycosaminoglycans in various organs, leading to tissue damage. Mucopolysaccharidoses include eight individual disorders (IS [Scheie syndrome], IH [Hurler syndrome], II, III, IV, VI, VII and IX). They have autosomal-recessive transmission with the exception of mucopolysaccharidosis II, which is X-linked. Each individual disorder has a wide spectrum of phenotypic variation, depending on the specific mutation, from very mild to very severe. The skeletal and central nervous systems are particularly affected. The typical clinical presentation includes organomegaly, dysostosis multiplex with short trunk dwarfism, mental retardation and developmental delay. In this article, we review the neuroimaging manifestations of the different types of mucopolysaccharidoses including the dysostosis multiplex of the skull and spine as well as the various central nervous system complications. These include white matter injury, enlargement of the perivascular spaces, hydrocephalus, brain atrophy, characteristic enlargement of the subarachnoid spaces as well as compressive myelopathy. The correlation between several of the neuroimaging features and disease severity remains controversial, without well-established imaging biomarkers at this time. Imaging has, however, a crucial role in monitoring disease progression, in particular craniocervical junction stenosis, cord compression and hydrocephalus, because this allows for timely intervention before permanent damage occurs.

Spinal cord issues in adult patients with MPS: transition of care survey.

PURPOSE: This study aims to raise awareness of the need for research and appropriate guidelines for managing spinal cord issues in adult patients with mucopolysaccharidosis (MPS) and transition of these patients from pediatric to adult care. METHODS: Pediatric/adult neurosurgeons, orthopedic spine surgeons, and treating physicians with expertise in metabolic disorders and spinal cord issues were invited to complete a survey to assess their experience with spinal cord problems in MPS and their opinion on transitioning routes from pediatric to adult care. RESULTS: Twenty specialists completed the survey; 16 had treated spinal cord issues in patients with MPS. Foramen magnum and cervical stenosis (87%), atlanto-axial instability (67%), and lumbar spine instability (33%) were the main spinal cord issues encountered; 28% had treated adult patients for one or more spinal cord issues. In 40% of cases, this concerned an intervention or procedures performed during childhood. The main specialist responsible for the care of adult patients with MPS differed considerably between institutions and included both pediatric and adult specialists (30% pediatric neurosurgeons, 10% pediatric spine orthopedic surgeons, 30% adult spine neurosurgeons, 20% general adult surgeons). The preferred option (> 50%) for the transition of care was an interdisciplinary team of pediatric and adult specialists. CONCLUSIONS: Further work needs to be done to address problems of managing spinal cord issues in adult patients with MPS. Currently, the responsibility for the care of patients with MPS with spinal cord issues is inconsistent. The best strategy for transitioning these patients from pediatric to adult care is likely an interdisciplinary approach.

Quantitative neuroimaging in mucopolysaccharidoses clinical trials.

The mucopolysaccharidosis (MPS) disorders are rare lysosomal storage disorders caused by mutations in lysosomal enzymes involved in glycosaminoglycan (GAG) degradation. The resulting intracellular accumulation of GAGs leads to widespread tissue and organ dysfunction. In addition to somatic signs and symptoms, patients with MPS can present with neurological manifestations such as cognitive decline, behavioral problems (e.g. hyperactivity and aggressiveness), sleep disturbances, and/or epilepsy. These are associated with significant abnormalities of the central nervous system (CNS), including white and gray matter lesions, brain atrophy, ventriculomegaly, and spinal cord compression. In order to effectively manage and develop therapies for MPS that target neurological disease, it is important to visualize and quantify these CNS abnormalities. This review describes optimal approaches for conducting magnetic resonance imaging assessments in multi-center clinical studies, and summarizes current knowledge from neuroimaging studies in MPS disorders. The content of the review is based on presentations and discussions on these topics that were held during a meeting of an international group of experts.

Neuroimaging Findings in Patients with Mucopolysaccharidosis: What You Really Need to Know.

Mucopolysaccharidosis (MPS) is an inherited metabolic disease and a member of the group of lysosomal storage disorders. Its hallmark is a deficiency of lysosomal enzymes involved in the degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs). The products of GAG degradation accumulate within lysosomes and in the extracellular space, thereby interfering with the degradation of other macromolecules. This process leads to chronic degeneration of cells, which in turn affects multiple organs and systems. There are seven distinct types of MPS (I, II, III, IV, VI, VII, and IX), which are divided into subtypes according to the deficient enzyme and the severity of the clinical picture. Although clinical manifestations vary considerably among the different types of MPS, the central nervous system (CNS) is characteristically affected, and magnetic resonance (MR) imaging is the method of choice to evaluate brain and spinal cord abnormalities. Enlarged perivascular spaces, white matter lesions, hydrocephalus, brain atrophy, cervical spinal canal stenosis with or without spinal cord compression and myelopathy, and bone abnormalities in the skull and spine (dysostosis multiplex) are typical imaging findings described in the literature and reviewed in this article. The differential diagnosis of MPS is limited because the constellation of imaging findings is highly suggestive. Thus, radiologists should be aware of its typical neuroimaging findings so they can recognize cases not yet diagnosed, exclude other metabolic diseases, monitor CNS findings over time, and assess treatment response. (©)RSNA, 2016.

Use of new imaging in detecting and monitoring ocular manifestations of the mucopolysaccharidoses.

The aim of this review is to summate the eye involvement in patients with mucopolysaccharidoses (MPS) using current ocular imaging techniques, their advantages and disadvantages and how they may aid diagnosis, management and monitoring. We critically reviewed the current literature surrounding MPS and recent imaging technology as well as histology. Primary searches of PubMed and Web of Science were performed. We reviewed all papers on the topic published and summarized the findings of each medical device as well as the advantages and disadvantages of using these for the MPS patient. We discussed the potential of each of these devices to monitor potential ocular pathology in the MPS cohorts in the order of MPS subtype. We reviewed imaging techniques involving use of the Iris Camera, Pentacam, Optical Coherence Tomography (OCT) as well as ultrasound and Heidelberg OCT. The need for reliable objective quantification of eye findings in MPS has led to utilization of new imaging technologies described here, and future use will enhance our understanding of the unique eye features in MPS. In particular, we note that the Pentacam and iris camera are able to provide objective measurements of corneal haze and monitor ocular response to treatment.