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Introduction: Gibbus deformity has been documented as a common musculoskeletal abnormality in mucopolysaccharidosis type I (Hurler syndrome, MPS IH), and its recognition often leads to the diagnosis of MPS IH. While the incidence has been described, the progression of gibbus deformities is not well known. Here we describe the natural history of gibbus deformity in a single center patient population using serial spinal MRI scans., Methods: All spinal MRI scans in MPS IH patients were retrospectively reviewed. The presence, spinal location, and angulation of the gibbus deformities were collected. The angles between the superior endplate of the superior normal vertebral body and the inferior endplate of the inferior normal vertebral body were measured., Results: 24 of 47 patients (51%) were found to have cervico-thoracic deformity on their cervical MRI scans, and 19 of those 24 (79%) patients were found to have progressive cervico-thoracic deformity with average change of angle of 17.1 degrees [range 3.9, 62.8] over 5.3 years. 7 of 8 patients who had thoraco-lumbar MRI were found to have thoraco-lumbar deformity, and 4 of those 7 patients (57%) were found to have progressive thoraco-lumbar deformity with the average increase angle of 16.7 degrees [range 3.3, 47.1] over an average of 4.1 years., Conclusion: We found out that baseline spinal measurement cannot reliably predict the progression as multiple patients with normal alignment eventually developed severe deformity, whereases patients with severe deformity did not progress to require surgical intervention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention., Methods: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements., Results: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age., Conclusions: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler-Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural history of cardiac abnormalities in treatment-naïve individuals enrolled in the international Mucopolysaccharidosis Type I Registry. Interrogation of echocardiography data (presence of cardiac valve regurgitation and/or stenosis; measurements of left ventricular chamber dimensions in diastole and systole, diastolic left ventricular posterior wall and interventricular septal thicknesses and ventricular systolic function (shortening fraction)) showed that mitral regurgitation was the most common and earliest finding for individuals with both severe (58.3%, median age 1.2 years) and attenuated (74.2%, median age 8.0 years) disease. Left-sided valve stenosis was also common in individuals with attenuated disease (mitral 30.3%; aortic 25%). Abnormal ventricular wall and septal thickness (Z-scores ≥2) were observed early in both phenotypes. Z-scores for diastolic left ventricular posterior wall and interventricular septal thicknesses increased with age in the severe phenotype (annualised slopes of 0.2777 [p = 0.037] and 0.3831 [p = 0.001], respectively); a similar correlation was not observed in the attenuated phenotype (annualised slopes of -0.0401 [p = 0.069] and -0.0029 [p = 0.875], respectively). Decreased cardiac ventricular systolic function (defined as shortening fraction <28%) was uncommon but, when noted, was more frequent in infants with the severe phenotype. While cardiac abnormalities occur early in both severe and attenuated mucopolysaccharidosis type I, the pattern of valve dysfunction and progression of ventricular abnormalities vary by phenotype.

The correct diagnosis is fundamental for the appropriate treatment to be employed in a particular pathology. The best treatment is not the one that solves only local problems, fragmenting the patient, and therefore, it is necessary to integrate the entire systemic condition of the individual before initiating any local treatment. This context inevitably requires dentistry to participate in a multidisciplinary approach, where the role of the dentist is expanded in concepts that encompass ethics, human dignity, and professional valorization. This article describes a clinical case of a patient with mucopolysaccharidosis type I, whose treatment of cystic lesions present in the mandible was exclusively performed through marsupialisation. The objective of this study is to demonstrate, within the complexity of this rare syndrome, the difficulties of diagnosis and the need for evaluation of the patient beyond the limits of the oral cavity, as well as to report two cases of large dentigerous cysts, surgically treated conservatively through marsupialisation, without the need for re-approach for enucleation and without recurrences over a 20-year period.

Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder characterized by the deficiency of the alpha-L-iduronidase enzyme necessary for the degradation of glycosaminoglycans (GAG) in the lysosome. Hurler syndrome is the most severe form of MPS I, manifesting as multiorgan dysfunction, cognitive delay, and death, usually within ten years if left untreated. Hematopoietic stem cell transplantation (HSCT) is the optimal treatment option, providing a permanent solution to enzyme deficiency and halting cognitive decline; however, the HSCT complications transplantation-associated thrombotic microangiopathy (TA-TMA) and graft-versus-host disease (GVHD) are known risk factors for bloodstream infection (BSI). BSI is a serious complication of HSCT, contributing to poor outcomes and transplantation-related morbidity. There are little data evaluating BSI after HSCT in the Hurler syndrome population. We performed a retrospective analysis of patients with Hurler syndrome who underwent HSCT at our center between 2013 and 2020 to determine the incidence of BSI within the first year post-transplantation. Patient BSI data were collected through the first year post-HSCT. Variables including patient demographics and transplantation-related characteristics were collected, including information on BSI and mortality. Twenty-five patients with a total of 28 HSCTs were included in the analysis; the majority (n = 17; 68%) were male, with a median age of 1.1 years (interquartile range, .35 to 1.44 years) at the time of transplantation. The most common graft source was cord blood (n = 15; 54%), followed by bone marrow (n = 13; 46%), with the majority from matched unrelated donors (n = 14; 52%) and mismatched unrelated donors (n = 13; 44%). Sixteen BSIs were diagnosed in 12 patients (48%). Most infections (n = 7; 43.8%) were diagnosed in the first 20 days post-transplantation, with fewer infections observed at later time points. Seven of the 9 Hurler patients diagnosed with TA-TMA (78%) also had a BSI. The incidence rate of BSIs in Hurler patients (n = 12; 48%) was higher than the rates reported in the general pediatric HSCT population at 1-year post-transplantation (15% to 35%). Given the high rate of both TA-TMA and a BSI in Hurler patients, we suspect a possible correlation between the 2. Additionally, due to the time it takes for GAG levels to normalize post-HSCT in Hurler patients, it is reasonable to suspect that the high BSI rates in these patients are linked to their Hurler diagnosis. These findings bring awareness to possible disease-related factors contributing to high BSI rates in the Hurler population post-HSCT., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Posterior fossa "horns" caused by internal hypertrophy of the occipitomastoid sutures are one of the more recently defined cranial abnormalities described in mucopolysaccharidoses, especially in Hurler Syndrome. However, details of this finding, including the development and natural history, are not well-understood. Two hundred eighty-six brain MR imaging studies of 61 patients with mucopolysaccharidosis I-Hurler syndrome treated at single institution between 1996 and 2015 were studied. Posterior fossa horn height was measured as the perpendicular distance from the tip of the horn to the expected curvature of the occipital inner table. Fifty-seven of the 61 patients (93.4%) had evidence of posterior fossa horns on at least one occasion. The initial average height of the right horn was 4.5 mm, and the left horn, 4.7 mm. Most of the posterior horns regressed before transplantation in our cohort, though the exact age was variable among the patients. Nearly all patients in our cohort had posterior fossa horns, and these horns regressed with age. The regression of the horns frequently started before transplantation. This trend has not been previously described, and it may suggest unknown effects of mucopolysaccharidosis on skull development., (© 2023 by American Journal of Neuroradiology.)

Purpose: Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by a defect in the enzyme alpha-L-iduronidase. Glycosaminoglycan accumulation causes ocular involvement such as corneal clouding or pigmentary retinopathy. Here we report bilateral macular cysts in mucopolysaccharidosis type I (MPS I) that responds to nepafenac treatment., Methods: Retrospective case report., Results: A 27-year-old woman with MPS I (Scheie phenotype) was complaining of slightly blurred vision. She had been on alpha-L-iduronidase enzyme replacement therapy for ten years. Best-corrected visual acuity was 20/25 in both eyes. Biomicroscopy was normal. Dilated fundus examination revealed pigmentary retinopathy. Optical coherence tomography (OCT) detected macular cysts in inner and outer nuclear layers, with preservation of ellipsoid zone and IS/OS line. There was no dye leakage on fluorescein angiography. Macular cysts regressed partially after one month with topical nepafenac 0.1% four times a day. BCVA improved to 20/20 in both eyes., Conclusions: This is the first report of bilateral macular cysts that was demonstrated with OCT and treated with topical nepafenac in a patient with MPS I. Because the symptoms of our patient were mild, large-scaled cohort studies are required to ascertain the real prevalence of macular cysts in MPS I. It may also be beneficial to do more research on the possible benefits of nepafenac on the retinal manifestations of MPS.

Hydrocephalus is one of the earliest manifestations of mucopolysaccharidosis I-Hurler syndrome, and delayed treatment of hydrocephalus can lead to neurocognitive delay or even death. Optic nerve sheath diameter has been established as a noninvasive measurement to detect elevated intracranial pressure. This study aimed to establish correlations between optic nerve sheath diameter and opening pressure. Forty-nine MR images and opening pressures in patients with mucopolysaccharidosis I-Hurler syndrome were retrospectively reviewed from 2008 to 2020. The optic nerve sheath diameter was measured 3 mm posterior to the posterior margin of the globe (retrobulbar) and 10 mm anterior to the optic foramen (midpoint segment), and the average was taken between the 2 eyes. Opening pressure was measured with the patient in the lateral decubitus position with controlled end-tidal CO 2 on the same day as the MR imaging. The average retrobulbar optic nerve sheath diameter was 5.33 mm, higher than the previously reported measurement in healthy controls, in patients with idiopathic intracranial hypertension, and there was a positive correlation between age and the optic nerve sheath diameter measured at the retrobulbar or midpoint segment (retrobulbar segment, R 2 = 0.27, P  < .01; midpoint segment, R 2 = 0.20, P  < .01). However, there was no correlation between retrobulbar or midpoint segment optic nerve sheath diameter and opening pressure (retrobulbar segment, R 2 = 0.02, P = .17; midpoint segment, R 2 = 0.03, P  < .12). This study shows a higher average optic nerve sheath diameter in patients with mucopolysaccharidosis I-Hurler syndrome than in healthy controls regardless of the location of the measurement. However, the degree of optic nerve sheath dilation does not correlate with opening pressure, suggesting that increased optic nerve sheath diameter is an ocular manifestation of mucopolysaccharidosis I-Hurler syndrome itself rather than a marker of elevated intracranial pressure., (© 2023 by American Journal of Neuroradiology.)

Purpose: The purpose of this study was to report the long-term surgical and visual outcomes of patients with mucopolysaccharidoses (MPS) after big bubble deep anterior lamellar keratoplasty (BB-DALK)., Methods: This was a retrospective case series of patients with MPS who underwent BB-DALK at a single academic institution. All patients had corneal clouding secondary to MPS limiting visual acuity for which keratoplasty was indicated. Each patient was evaluated and underwent surgery by a single surgeon. Reported data included age at keratoplasty, sex, MPS type, best spectacle-corrected visual acuity, change in pachymetry, ocular comorbidities, surgical complications, and MPS-related medication use., Results: Outcomes of 12 eyes from 7 patients with MPS type I (Hurler, Scheie, and Hurler-Scheie) are reported using the newest nomenclature. The mean follow-up was 5.58 years (range: 1-10 years). All cases underwent BB-DALK with a type 1 big bubble during the surgery. Two cases (16.6%) required rebubbling because of partial Descemet membrane detachment. One case was complicated by a suture abscess and required a penetrating keratoplasty. No episodes of rejection occurred. Statistically significant improvement in the best spectacle-corrected visual acuity (from a mean 0.85-0.33 logarithm of the minimum angle of resolution, P = logarithm of the minimum angle of resolution 0.0054) and pachymetry (mean reduction of -145.4 μm, P = 0.0018) was observed., Conclusions: BB-DALK seems to be an acceptable long-term surgical option in patients with MPS. Our findings suggest that this technique is reproducible and can achieve clear corneal grafts with good visual results on a long-term follow-up., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A physical symptom score (PSS) for the mucopolysaccharidosis (MPS) disorders has been developed to quantitate the somatic burden of disease across multiple organ systems. Studies have demonstrated the sensitivity and its relationship to age, IQ and adaptive functioning of the PSS in older children. With the onset of newborn screening, there is an increased need to characterize the somatic symptoms in the earliest stages of life, especially for young children under 36 months of age. Consequently, a new scale, Infant Physical Symptom Score (IPSS), was developed to score physical symptoms in infants and toddlers., Objective: Part I. To create a measure to quantify somatic burden in patients with MPS disorders under 36 months of age. The IPSS assess outcomes and changes in somatic disease in individuals with MPS disorders diagnosed very early in life. Part II. To determine the relationship between IPSS and other measures to evaluate its validity and utility, a) we evaluated the relationship between the IPSS and PSS in the same patients with MPS I over time to determine if the two scales are measuring the same concepts, and b) we evaluated the association between IPSS and a functional adaptive measure over time with a focus on the age at first treatment (under 36 months) to determine if the IPSS has predictive value., Methods: Part I. The Infant Physical Symptom Score (IPSS) for the infant population in MPS disorders was established using data from 39 patients enrolled in the Lysosomal Disease Network longitudinal MPS I study (U54NS065768). All of these patients had Hurler syndrome (MPS IH) and underwent hematopoietic stem cell transplant (HSCT) at the University of Minnesota. Items for the IPSS were selected by reviewing CRFs prepared for the MPS I longitudinal study and examining medical records of these patients prior to HSCT based on the knowledge gained from the development of the PSS. Part II. Of those 39 patients, a subset of 19 were all seen 9 to 12 years post HSCT. Having retrospectively calculated their IPSS prior to HSCT, we categorized them by age at HSCT, and examined their most recent PSS along with Composite and Daily Living Skills scores on the Vineland Adaptive Behavior Scales - Second Edition (VABS-II)., Results and Conclusion: The total score on the IPSS collected prior to transplant differed by patient's age at transplant, as expected in this progressive condition. Those transplanted at ≤12 months of age had a mean score of 7.4, which was significantly lower, suggesting less somatic disease burden, compared to those transplanted at >12 to ≤24 months (mean 11.8) and > 24 to ≤36 months (mean 13.6). Higher IPSS reflects more evidence of somatic disease burden and lower IPSS reflects less evidence of disease burden. Nine to 12 years later, the severity level as measured by the PSS was comparable to severity on the IPSS suggesting that the two scales are measuring similar concepts. Retrospectively calculated pre-transplant IPSS were negatively associated with higher VABS-II Composite scores 9-12 years later (p value-0.015) and to a lesser extent Daily Living Skills scores (p value-0.081). We conclude that the IPSS appears to be a useful approach to quantifying the somatic disease burden of MPS IH patients under 36 months of age., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed., Competing Interests: Declaration of Competing Interest Dr. A Broomfield declares travel assistance from Takeda Pharmaceutical, Sanofi and Biomarin Pharmaceutical and consulting fees from Sanofi, unrelated to this work. Dr. A Ghosh declares travel assistance from Biomarin Pharmaceutical and honoraria from Alexion Pharmaceuticals, unrelated to this work. Dr. KM Stepien has received travel grants from BioMarin, Genzyme, Alexion, Takeda Pharmaceutical and honoraria from Biomarin Pharmaceutical Chiesi, Sanofi, Orchard Therapeutics and Takeda unrelated to this work. K Tylee declares prior travel assistance from Biomarin Pharmaceutical, unrelated to this work. Dr. S Jones declares consultancy for Genzyme, Shire, Alexion Pharmaceuticals, Orchard Therapeutics, Denali Therapeutics, and Ultragenyx Pharmaceutical, unrelated to this work. All other authors declare no conflict of interest., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Hurler syndrome-associated keratopathy is an exceedingly rare corneal disorder that requires corneal transplantation in advanced stages. Precise assessment of the corneal condition is necessary for deciding which type of keratoplasty (i.e., deep anterior lamellar or penetrating) should be proposed. We aimed to confront the results of multimodal imaging with those of histology in a case of Hurler syndrome-associated keratopathy., Case Presentation: A 16-year-old patient with Hurler's syndrome treated with hematopoietic stem cell transplantation was referred for decreased vision related to advanced keratopathy. The patient was treated with deep anterior lamellar keratoplasty (DALK) in both eyes with uncomplicated outcome. Visual acuity improved from 0.1 (20/200) preoperatively to 0.32 (20/63) and 0.63 (20/32) after transplantation. The corneal endothelial cell density was 2400 cells/mm 2 in both eyes 3 years after transplantation. In vivo confocal microscopy (IVCM) and spectral domain optical coherence tomography (SD-OCT) were performed preoperatively. The corneal buttons retrieved during keratoplasty were processed for histology. In SD-OCT scans, corneal opacities appeared as diffuse stromal hyperreflectivity associated with increased corneal thickness. IVCM showed diffuse cytoplasmic granular hyperreflectivity and rounded/ellipsoid aspects of keratocytes, presence of small intracellular vacuoles, and hyperreflective epithelial intercellular spaces. Bowman's layer was thin and irregular. The corneal endothelium was poorly visualized but no endothelial damage was observed. Histology showed irregular orientation and organization of stromal lamellae, with the presence of macrophages whose cytoplasm appeared clear and granular. A perinuclear clear halo was visible within the epithelial basal cells. Bowman's layer featured breaks and irregularities., Conclusions: The observed corneal multimodal imaging features in mucopolysaccharidosis-related keratopathy were concordant with histology. Compared with standard histology, multimodal imaging allowed additional keratocyte features to be observed. It revealed both morphological and structural changes of all corneal layers but the endothelium. This information is essential for therapeutic management which should include DALK as the first-choice treatment in case of impaired visual acuity.

Objectives: The mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders with multisystemic and highly variable clinical manifestation. ENT symptoms are common and early signs of MPS. The most common ENT diagnoses are chronic/recurrent rhinosinusitis, acute otitis media, otitis media with effusion, hearing loss and airway obstruction., Methods: A single-centre retrospective chart review of 61 patients (36 M/25F) with different MPS subtypes (MPS I (n = 15), MPS II (n = 10), MPS III (n = 17), MPS IV (n = 15) and MPS VI (n = 4)) was conducted. The age of ENT presentation and frequency of ENT symptoms, surgeries and their distribution among MPS subtypes was studied. The relationship between ENT presentation, first ENT surgery and the age of diagnosis was also evaluated., Results: Median age at the first ENT manifestation was 2.8 years, median age at MPS diagnosis 4.1 years. The great majority of patients (90%) manifested at least one ENT diagnosis; often before the diagnosis of MPS (75%). Chronic/recurrent rhinosinusitis was the most prevalent ENT diagnosis (77%), followed by upper airway obstruction (65%) and hearing loss (53%). Chronic/recurrent rhinosinusitis was the first ENT symptom to appear (median age 2.2 years), followed by otitis media with effusion (3.7 years) and hearing loss (4.5 years). At least one ENT surgery was performed in 57% of patients; in 69% before MPS diagnosis was established. Median age of the first ENT surgery was 4.1 years. ENT symptoms and surgical procedures were earliest present in MPS II., Conclusions: Our study documents high and early occurrence of various otolaryngologic symptoms in MPS and thus highlights the role of ENT specialist in prompt diagnosis of these rare diseases and their long-term management., Competing Interests: Declaration of competing interest MM has received the lecture honoraria from Takeda, Genzyme and Biomarin. LM has received the lecture honoraria from Takeda. PJ has received the lecture honoraria from Genzyme and Takeda. The declared collaboration had no impact on the intention to prepare the study or on its content., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mucopolysaccharidosis type I is a genetic disorder with impaired glycosaminoglycan degradation. Cardiac pathologic involvement in this subset of patients is predominantly valvular heart disease. Valvular heart disease seen in these patients will most likely require surgical intervention in their lifetime. Only a limited amount of reports are dedicated to the cardiac surgical management of mucopolysaccharidoses. We present the case of a 32-year-old female with Hurler-Scheie syndrome who required multiple valve replacements due to progression of valvular dysfunction and decline in the quality of life. Multidisciplinary evaluation and discussion early are crucial for quality of life optimization in this cohort of patients.

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disease characterized by severe phenotypes, including corneal clouding. MPS I is caused by mutations in alpha-l-iduronidase (IDUA), a ubiquitous enzyme that catalyzes the hydrolysis of glycosaminoglycans. Currently, no treatment exists to address MPS I corneal clouding other than corneal transplantation, which is complicated by a high risk for rejection. Investigation of an adeno-associated virus (AAV) IDUA gene addition strategy targeting the corneal stroma addresses this deficiency. In MPS I canines with early or advanced corneal disease, a single intrastromal AAV8G9-IDUA injection was well tolerated at all administered doses. The eyes with advanced disease demonstrated resolution of corneal clouding as early as 1 week post-injection, followed by sustained corneal transparency until the experimental endpoint of 25 weeks. AAV8G9-IDUA injection in the MPS I canine eye with early corneal disease prevented the development of advanced corneal changes while restoring clarity. Biodistribution studies demonstrated vector genomes in ocular compartments other than the cornea and in some systemic organs; however, a capsid antibody response was detected in only the highest dosed subject. Collectively, the results suggest that intrastromal AAV8G9-IDUA therapy prevents and reverses visual impairment associated with MPS I corneal clouding., (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by α-L-iduronidase deficiency, resulting in accumulation of glycosaminoglycans (GAG). Ophthalmological manifestations are common in MPS I patients and often lead to visual impairment. Accumulation of GAG in corneal or retinal tissues reduces vision causing corneal opacity and neurosensory complications. One available treatment for MPS I patients is enzyme replacement therapy (ERT), but the results of such treatment on eye disease are still debatable. Therefore, we aimed to determine the progression of ocular manifestations as well as the effectiveness of intravenous ERT in MPS I., Methods: Corneal and retinal analyses were perform in eyes from 2- to 8-month normal and MPS I mice. Some MPS I mice received ERT (1.2 mg/kg of laronidase) every 2 weeks from 6 to 8 months and histological findings were compared with controls. Additionally, cornea from two MPS I patients under ERT were evaluated., Results: Mouse corneal tissues had GAG accumulation early in life. In the retina, we found a progressive loss of photoreceptor cells, starting at 6 months. ERT did not improve or stabilize the histological abnormalities. MPS I patients, despite being on ERT for over a decade, presented GAG accumulation in the cornea, corneal thickening, visual loss and needed corneal transplantation., Conclusion: We provide data on the time course of ocular alteration in MPS I mice. Our results also suggest that ERT is not effective in treating the progressive ocular manifestations in MPS I mice and fails to prevent corneal abnormalities in patients., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recombinant human alpha-L-iduronidase). While hematopoietic stem cell transplantation treats neurological symptoms, this therapy is not generally offered to attenuated MPS I patients. This study is a randomized, open-label, controlled pilot study of intrathecal laronidase in eight attenuated MPS I patients with cognitive impairment. Subjects ranged between 12 years and 50 years old with a median age of 18 years. All subjects had received intravenous laronidase prior to the study over a range of 4 to 10 years, with a mean of 7.75 years. Weekly intravenous laronidase was continued throughout the duration of the study. The randomization period was one year, during which control subjects attended all study visits and assessments, but did not receive any intrathecal laronidase. After the first year, all eight subjects received treatment for one additional year. There was no significant difference in neuropsychological assessment scores between control or treatment groups, either over the one-year randomized period or at 18 or 24 months. However, there was no significant decline in scores in the control group either. Adverse events included pain (injection site, back, groin), headache, neck spasm, and transient blurry vision. There were seven serious adverse events, one judged as possibly related (headache requiring hospitalization). There was no significant effect of intrathecal laronidase on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period. A five-year open-label extension study is underway., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To report successful management of corneal clouding associated with Hurler-Scheie syndrome with deep anterior lamellar keratoplasty (DALK) undergoing concurrent enzyme replacement therapy (ERT)., Methods: A 13-year-old boy with Hurler-Scheie syndrome (MPS I-HS) presented with corneal clouding in both eyes. He was on ERT with laronidase (Aldurazyme; Genzyme, Cambridge, MA) and had a visual acuity of 20/32 in both eyes. Seven years later, visual acuity in his left eye decreased to counting fingers and DALK was performed for vision recovery. Two years later, visual acuity in his right eye decreased to 20/100 and DALK was performed., Results: At his last visit, which was 3 years after right eye DALK and 5 years after left eye DALK, the grafts were clear and the corrected visual acuity in his right and left eyes was 20/30 and 20/25, respectively., Conclusions: The present case highlights the possible effectiveness of DALK in patients with mucopolysaccharidosis (MPS)-related corneal stromal opacification, treated with ERT.

Umbilical cord blood (UCB) is the preferred donor cell source for children with Hurler syndrome undergoing transplant, and its use has been associated with improved "engrafted survival" rates. However, as in other pediatric recipients of UCB transplants for nonmalignant disease, immune-mediated cytopenia (IMC) is a significant complication. This article describes 8 episodes of IMC in 36 patients with Hurler syndrome undergoing UCB transplant. The incidence of IMC was increased in those with a higher preconditioning absolute lymphocyte count and in those conditioned with fludarabine-containing regimens rather than cyclophosphamide, and it included red cell alloantibodies directed at cord blood group antigens that are novel to the recipient. In several cases, IMC was a precursor to immune-mediated complete graft rejection. We describe IMC as part of a spectrum of graft rejection by a residual competent host immune system and a forme fruste of complete graft rejection., (© 2019 by The American Society of Hematology.)

Mucopolysaccharidoses (MPS) are a subgroup of lysosomal storage disorders. The underlying mechanism of MPS disorders are deficiency in specific enzymes which leads to accumulation of partially degraded glycosaminoglycans (GAGs) in various tissues. A wide variety of manifestations are reported but musculoskeletal complaints are common among them. In milder forms of MPS, musculoskeletal complaints are presenting symptoms. Delays in diagnosis due to unspecific and mild symptoms is common. Misdiagnosis of MPS as juvenile idiopathic arthritis and other inflammatory arthritis disorders is frequent. Early diagnosis and treatment prevents irreversible cellular damages and is a key factor in efficacy of enzyme replacement therapy. In this study we described two MPS patients with musculoskeletal complaints who were not diagnosed for a period of time. Although musculoskeletal manifestation are common in a variety of clinical conditions, their presence at low ages or co-occurrence of other manifestations (such as cardiac, respiratory, neurologic, etc.) in multiple systems should prompt evaluation of patients for MPS and other metabolic disorders. The rheumatologists' awareness on MPS should be promoted to achieve timely diagnosis and subsequent early treatment.

Background: Mucopolysaccharidosis type I (MPS I) results in significant disease burden and early treatment is important for optimal outcomes. Recognition of short stature and growth failure as symptoms of MPS I among pediatric endocrinologists may lead to earlier diagnosis and treatment., Case Presentation: A male patient first began experiencing hip pain at 5 years of age and was referred to an endocrinologist for short stature at age 7. Clinical history included recurrent respiratory infections, sleep apnea, moderate joint contractures, mild facial dysmorphic features, scoliosis, and umbilical hernia. Height was more than - 2 SD below the median at all time points. Growth velocity was below the 3rd percentile. Treatment for short stature included leuprolide acetate and recombinant human growth hormone. The patient was diagnosed with MPS I and began enzyme replacement therapy with laronidase at age 18., Conclusions: The case study patient had many symptoms of MPS I yet remained undiagnosed for 11 years after presenting with short stature. The appropriate path to MPS I diagnosis when patients present with short stature and/or growth failure plus one or more of the common signs of attenuated disease is described. Improved awareness regarding association of short stature and growth failure with attenuated MPS I is needed since early identification and treatment significantly decreases disease burden.

Background: Hip dysplasia is common in mucopolysaccharidosis type-1H (MPS-1H) patients, but its morphology is not completely understood. No magnetic resonance imaging (MRI)-based studies have been reported in the literature. The purpose of this study was to improve knowledge of hip dysplasia pathology by describing the hip morphology of these patients in MRI scans, plain radiographs, and arthrograms., Methods: We performed a retrospective chart review of 18 MPS-1H patients. Supine anteroposterior pelvic radiographs of 36 hips and MRI scans of 18 hips were analyzed. Six arthrographs were also available., Results: Plain radiographs were available for 18 patients. The mean age was 6.0 (SD=3.8) years. The mean acetabular index (AI) was 36.2 degrees (SD=5.8), and the mean migration percentage was 59.0% (SD=17.2). MRI data were available for 9 patients. The MRI findings were compared with the radiographs of the same patient. The mean AI (39.3 degrees, SD=5.8) was confirmed by the MRI findings (39.1 degrees, SD=5.5). The migration percentage was lower in the MRI scans than in the radiographs. Radiologically, the center-edge angle was negative in all patients, with a mean of -16.8 degrees (SD=7.9), and the MRI images produced a more negative value (-19.6 degrees, SD=7.6). The soft tissue coverage of the femoral head was described with the inclusion of the cartilaginous roof and labrum. The cartilaginous AI was 22.4 degrees (SD=7.5), and the labral AI was 13.5 degrees (SD=6.7). All 6 arthrograms revealed stability during dynamic testing., Conclusions: This study provides the first description of hip morphology in MPS-1H patients through MRI-based data. The cartilaginous coverage of the hip was increased compared with that of healthy children. The use of radiography alone may lead to a misunderstanding of hip morphology. MRI and arthrogram is highly recommended if surgery is considered.

Purpose: To determine whether the ocular phenotype in patients with mucopolysaccharidosis type I (MPSI) Hurler is affected by the efficacy of previous haemopoietic stem cell transplantation (HSCT)., Design: A retrospective cohort study of patients with MPSI who had undergone treatment with HSCT., Methods: Ocular phenotype was documented for each patient and compared to levels of biomarkers representing efficacy of previous transplantation., Main Outcome Measures: Assessment of visual acuity (VA), severity of corneal clouding and the presence of optic neuropathy or retinopathy. Biomarker assessment included dermatan sulphate/chondroitin sulphate (DS/CS) ratio and iduronidase enzyme level., Results: Severe corneal clouding was significantly greater in patients with lower iduronidase levels (p = 0.023) and raised DS/CS ratio (R 2  = 0.28 p = 0.043). Better VA was related to a higher iduronidase levels (R 2  = 0.15, p = 0.004) and lower DS/CS ratio (R 2  = 0.38, p = 0.001)., Conclusion: Improved ocular phenotypes in MPSI are associated with markers signifying efficacy of prior transplant. Early and effective HSCT may result in a better visual prognosis and reduction in ocular complications for patients with MPSI., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Hematopoietic cell transplantation is a life-saving procedure, but one associated with increasing long-term cardiovascular risk requiring frequent long-term follow-up. This therapy has significantly lengthened survival in mucopolysaccharidosis type IH (Hurler syndrome), a disease with known coronary artery involvement. Metabolic syndrome-a constellation of central obesity, high blood pressure, low high-density lipoprotein cholesterol, elevated triglycerides, and fasting blood glucose-is associated with increased cardiovascular risk, and occurs when any 3 or more of these 5 components is present within a single individual. The incidence of metabolic syndrome and its components is poorly defined after transplantation for Hurler syndrome. Chart review of all long-term survivors of hematopoietic cell transplantation for Hurler syndrome ≥9 years of age for factors comprising the metabolic syndrome: obesity, high blood pressure, low high-density lipoprotein cholesterol, elevated triglycerides, and fasting blood glucose. Sixty-three patients were evaluated, 20 of whom had components of the metabolic syndrome available for review. There was no significant difference in age at transplantation, sex, number of transplants, pretransplant radiation, or percent engraftment between those with and without these data. Median follow-up after transplantation for the 20 patients with data was 14.3 years. Only 1 (5%) patient of this group fulfilled the criteria for metabolic syndrome. Fifty-three percent of the patients had 1 or more components of metabolic syndrome: the most common was high blood pressure occurring in 40%. Metabolic syndrome is uncommon in this cohort of long-term survivors of hematopoietic cell transplantation for Hurler syndrome but almost half of the patients had 1 or more components of the syndrome, with high blood pressure being the most common. Further studies are needed to develop guidelines in this diagnosis as well as other nonmalignant diseases of children., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Hurler syndrome is an autosomal recessive mucopolysaccharidosis characterized by intralysosomal accumulation of glycosaminoglycan fragments, with cellular accumulation of distended lysosomes resulting in interference with normal cell function. One of the peripheral blood features of mucopolysaccharidoses is the presence of numerous, dark lilac granules within lymphocytes, monocytes, and neutrophils, also known at Alder-Reilly anomaly. Here we describe intracytoplasmic granules with haloes in mononuclear cells present in the cerebrospinal fluid of a 2-year-old boy with the diagnosis of Hurler syndrome, undergoing pretransplant evaluation for an unrelated donor cord blood stem cell transplant.

Gökay S, Kardaş F, Kendirci M, Sözeri B. Arthropathy-like findings and a carpal tunnel syndrome as the presenting features of Scheie syndrome: Three cases from the same family. Turk J Pediatr 2018; 60: 344-347. Mucopolysaccharidosis (MPS) type I is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme α-L-iduronidase. MPS I is divided into three subtypes based on the severity of symptoms: Hurler, Hurler-Scheie, and Scheie syndrome (severe, intermediate, and mild forms, respectively). Musculoskeletal involvement may be the only presenting sign in the patients with Scheie syndrome. We have reviewed three cases with prominent features of carpal tunnel syndrome (CTS) at the onset of their disease. Diagnosis was delayed in almost all cases (range 16-19 years). During one year of follow-up period, alleviations of the pain in the hands of patients were observed after enzyme replacement therapy. MPS type I should be considered in the differential diagnosis of the patients with CTS in the first and second decades of life, particularly with stiffness of the fingers and difficulty using the hands without an inflammatory component. An increased awareness of the disease may contribute to more accurate diagnosis, and patients may benefit from early intervention.

We describe 2 adult sisters with type I mucopolysaccharidosis (MPS) who underwent combined mitral and aortic valve replacement for mitral and aortic valve stenosis. One died early postoperatively and the other survived but had a repeat double-valve replacement 1 month after the first. We analyzed previously reported patients with MPS and valve replacement to learn of their outcomes. The study of our 2 patients and those previously reported suggests that valve replacement in patients with MPS should be viewed with extreme caution., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To characterize carpal tunnel syndrome (CTS) in patients with mucopolysaccharidosis I (MPS I)., Method: Data were included for patients with MPS I who had either nerve conduction examination that included a diagnosis of CTS or who had CTS release surgery. Although this represented a subset of patients with CTS in the MPS I Registry, the criteria were considered the most objective for data analysis., Results: As of March 2016, 994 patients were categorized with either severe (Hurler syndrome) or attenuated (Hurler-Scheie or Scheie syndromes) MPS I. Among these, 291 had a CTS diagnosis based on abnormal nerve conduction (n=54) or release surgery (n=237). Median ages (minimum, maximum) at first CTS diagnosis were 5 years 2 months (10mo, 16y 2mo) and 9y 11mo (1y 8mo, 44y 1mo) for patients with severe and attenuated MPS I respectively. Most patients had their first CTS diagnosis after MPS I diagnosis (94%) and treatment (hematopoietic stem cell transplant and/or enzyme replacement therapy) (74%). For 11% of patients with attenuated disease, CTS diagnosis preceded MPS I diagnosis by a mean of 7 years 6 months., Interpretation: CTS is a rare complication in pediatric patients and should alert medical care providers to the potential diagnosis of MPS I. Significant delays exist between diagnosis of CTS and MPS I for patients with attenuated disease., What This Paper Adds: There are significant delays in diagnosing carpal tunnel syndrome (CTS) in patients with mucopolysaccharidosis I (MPS I). Enzyme replacement therapy or hematopoietic stem cell transplant do not prevent the development of CTS. Testing for CTS in patients with MPS I is recommended to prevent irreparable damage. CTS in pediatric patients should alert physicians to potential diagnosis of MPS I., (© 2017 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Splenic rupture in the neonatal period is a rare condition that can be complicated by hemorrhagic shock. The symptoms are not very specific, rendering the diagnosis difficult and often delayed; sometimes only discovered at autopsy. We report five cases diagnosed in the Rhône-Alpes region of France. From these observations and from a review of the literature, the circumstances of the occurrence, the clinical signs, and the therapeutic possibilities are discussed. In the presence of severe anemia with pallor and abdominal distension, particularly in the context of a difficult birth, an abdominal ultrasound must be urgently performed and surgical management promptly considered., Conclusion: This pathology must be known to the neonatologist so that she/he can quickly evoke it, given that it can quickly become life-threatening. What is known: • Splenic rupture in the neonatal period is a rare condition that can be complicated by hemorrhagic shock and quickly lead to the death of the newborn. • The symptoms are not very specific, rendering the diagnosis difficult and often delayed. What is new: • This is the first publication bringing together as many clinical cases on the subject reporting in particular very serious cases to alert the clinician on this pathology and its diagnostic urgency. • We propose a clear therapeutic behavior to help the clinician in his daily practice.

Purpose: Children with Hurler syndrome (HS) develop carpal tunnel syndrome (CTS) owing to glycosaminoglycan deposition secondary to enzyme deficiency. Advancement in the treatment of the underlying enzyme deficiency now commonly includes peritransplant intravenous enzyme replacement therapy (ERT). The primary objective of this study was to determine if the use of limited ERT in addition to hematopoietic stem cell transplantation (HCT) for the treatment of children with HS reduces the incidence of surgical intervention for CTS compared with a cohort of historical controls treated with HCT alone. The secondary objectives were to evaluate the impact of demographic and transplant-related characteristics on the incidence of CTS. Lastly, the results of surgical treatment of CTS in HS are reported., Methods: Medical records for a historical group of 43 HS patients who underwent HCT alone (group 1) were compared with 31 HS patients who underwent HCT + ERT (group 2). Both groups were compared for genotype, age at transplant, sex, transplant graft source, median/ulnar nerve conduction study parameters as well as the incidence and treatment of CTS. Pre- and postoperative nerve conduction studies were compared for children treated surgically for CTS., Results: The cumulative incidence of CTS at 5 years for HS children treated with HCT + ERT was 51% compared with 47% for HS children treated with HCT alone. The incidence of CTS did not depend upon graft source, age at transplant, or sex. Median nerve conduction velocity for both sensory and motor potentials demonstrated significant improvement after carpal tunnel release., Conclusions: Although the administration of ERT prior to and for several months after HCT has become routine in our institution, our findings do not suggest this combined therapy is sufficient to decrease the development of CTS. Surgical intervention for median nerve compression remains the treatment of choice for CTS in HS children., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Premature death in untreated children with Hurler syndrome (HS) in the first decade of life is largely due to life-threatening cardiopulmonary complications. We examined the long-term survival and cardiopulmonary outcome in 54 children undergoing haematopoietic stem cell transplantation (HSCT) at the Royal Manchester Children's Hospital from 1985 to 2008. The median age at first HSCT was 15.1 months. Eighteen had graft failure and nine died after first HSCT. Of 18 patients with graft failure, 17 underwent second HSCT and the remaining one was lost to follow-up (LOF). Twelve were alive-and-engrafted after second HSCT. The overall survival at one year and 20-years was the same at 73.7%. Six children were followed up at the referral centers and excluded from cardiopulmonary endpoint review. Of the 33 evaluable children for the cardiopulmonary endpoints, nine (27.3%) had normal cardiac assessment. Of the four children on angiotensin-converting-enzyme inhibitors, two had mild cardiomyopathy and two had aortic valvular replacement. Twenty (60%) had mild/moderate mitral and/or aortic insufficiencies. Two had overnight hypoxia needing nocturnal non-invasive support. Enzyme level and donor chimerism are important predictors of long-term cardiac outcome.

Abstract: This case involves a 13-month-old male with Hurler syndrome. Due to oxygen desaturations during sleep, this patient was referred for polysomnography, which revealed severe mixed sleep apnea (apnea-hypopnea index [AHI] 72 events/h). Because sleep apnea in patients with Hurler syndrome is frequently attributed to upper airway obstruction, he was referred to otolaryngology. Prior to his evaluation by otolaryngology, he underwent ventriculoperitoneal (VP) shunt placement, which had been scheduled due to hydrocephalus on brain magnetic resonance imaging (MRI). After VP shunt placement, his oxygen desaturations during sleep resolved. Repeat polysomnogram revealed mild sleep apnea (AHI 1.9). The etiology of his sleep apnea was likely his hydrocephalus. This is the first report of a patient with Hurler syndrome with sleep apnea which markedly improved with ventriculostomy and VP shunt placement. This highlights the importance of considering neurological etiologies for sleep apnea in Hurler's patients, despite their predisposition for airway obstruction., (© 2016 American Academy of Sleep Medicine)

Inborn errors of metabolism (IEM) comprise an assorted group of inherited diseases, some of which are due to disordered lysosomal or peroxisomal function and some of which might be improved following hematopoietic cell transplantation (HCT). In these disorders the onset in infancy or early childhood is typically accompanied by rapid deterioration, resulting in early death in the more severe phenotypes. Timely diagnosis and immediate referral to an IEM specialist are essential steps in optimal management. Treatment recommendations are based on the diagnosis, its phenotype, rate of progression, prior extent of disease, family values, and expectations, and the risks and benefits associated with available therapies, including HCT. International collaborative efforts are of utmost importance in determining outcomes of therapy for these rare diseases, and have improved those outcomes significantly over the last decades. In this review, we will focus on the neurodevelopmental outcomes after HCT in IEM, providing an international perspective on progress, limitations, and future directions., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by deficiency of α-l-iduronidase. The otolaryngological findings include hearing loss, otorrhea, recurrent otitis, hypertrophy of tonsils and adenoid, recurrent rhinosinusitis, speech disorders, snoring, oral breathing and nasal obstruction., Objective: To evaluate the impact of enzymatic replacement therapy with laronidase (Aldurazyme(®)) in patients with mucopolysaccharidosis (MPS I), regarding sleep and hearing disorders, and clinical manifestations in the upper respiratory tract (URT)., Methods: Nine patients with MPS I (8 Hurler-Scheie, and 1 Scheie phenotypes) of both sexes, ages ranging between 3 and 20 years, were included in this study. Patients were evaluated between seven and 11 months before the treatment and between 16 and 22 months after the onset of the enzymatic replacement. They were all submitted to a clinical and otolaryngological evaluation, including nasofibroscopical, polysomnographic and audiologic exams., Results: The results' data showed decreasing of the frequency of ear, nose and throat infections, with improvement of the rhinorrhea and respiratory quality. No remarkable changes were observed regarding macroglossia and tonsil and adenoid hypertrophy. Audiometric and polysomnographic evaluations did not show statistical significance., Conclusion: Enzymatic replacement therapy in patients with mucopolysaccharidosis I provides control of recurrent URT infections, rhinorrhea and respiratory quality, however it is does not seem to improve audiologic and polisomnographic parameters, with no effect on adenoid and tonsils hypertrophy and macroglossia., (Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

The mucopolysaccharidosis (MPS) is a rare lysosomal storage disease. Glycosaminoglycans (GAG) accumulate in musculoskeletal system, connective tissues. Enlarged tongue, short immobile neck, and limited mobility of the cervical spine and temporomandibular joints render the airway management potentially risky. MPS children have high anesthetic risks, especially in airway management of emergency situations. The foreign-body aspiration requiring intervention with rigid bronchoscopy is an urgent and risky clinical situation. We present our experience with a challenging airway management with a three-year-old child with MPS who needed emergency bronchoscopy due to peanut aspiration.

Background: Hematopoietic stem cell transplants, alongside enzyme replacement therapy and good multi-disciplinary care, have dramatically improved the life expectancy in children with Mucopolysaccharidosis (MPS) I, with better objective and functional outcomes. Despite these improvements, children with both the attenuated (non-Hurler) and severe (Hurler) variants of the disease have marked residual morbidity. Children with MPS I suffer with head and neck disease including obstructive sleep apnoea and hearing loss. The impact of these on quality of life has been poorly researched and no previous work has been published looking at patients' perception of their own health, an important domain when considering the impact of treatment., Methods: This exploratory qualitative study aimed to discover the effect of head and neck disease, alongside that of MPS I as a whole, on the quality of life of affected children. A grounded theory approach was used to conduct this study. Children and their parents were invited to participate in semi-structured interviews. The transcribed interviews were coded and emergent themes explored until saturation occurred., Results: The families of eleven children with MPS I were interviewed, five with Hurler's and six with the attenuated non-Hurler's. Important themes to emerge were- the fear of dying associated with obstructive sleep apnoea, difficulties communicating at school due to the delayed acquisition of language, chronic pain and restricted mobility, physical differences and restricted participation in social activities such as sports secondary to the musculoskeletal disease burden. The overall theme running through the analysis was the desire to fit in with ones peers., Conclusion: Parents and children with MPS 1 worry about 'fitting-in' with broader society. The presence of airway disease has a profound impact on the emotional well being of parents whilst language delay and musculoskeletal disease have the biggest impact on the quality of life of the children themselves. It is important to understand the impact of MPS I on the quality of life of children and their families so that we may improve future treatment and management of this sub-group of children who have an increasing life span.

Background: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for young Hurler patients. Despite halting of neurocognitive decline and improvement of life expectancy, the beneficial effect on the skeletal system is limited. As orthopedic complications are one of the most disabling factors following HSCT, this points to the need for new treatment strategies. The study summarizes musculoskeletal manifestations in 19 transplanted Hurler patients., Methods: Data were obtained retrospectively. Patients' charts for physical examinations of the joint range of motion (JROM) of shoulders, elbows, hips and knees were reviewed. Radiographic evaluations of thorax, spine, pelvis and hands were performed. MRI scans of the craniocervical junction were analyzed to determine odontoid hypoplasia and the prevalence of craniocervical stenosis., Results: Nineteen Hurler patients (10 females, 9 males) with an average age of 8.1 years (range 2.5-23.8) at the latest follow-up, who underwent allogenic HSCT between 1991 and 2012, were assessed after an average follow-up period of 6.4 years (range 0.7-22.5). Seventeen patients achieved long-term engraftment, two developed graft failures. The majority of patients showed a steady state or improvements in the mobility of knees (31 %/63 %), hips (47 %/40 %) and elbows (56 %/38 %). However, shoulder abduction was impaired in ¾ of patients and showed the highest rate of progression (31 %). In patients with graft failure, progressive restrictions in JROM were noted. Assessments of the craniocervical junction by MRI showed stable or improved diameters in 67 % of patients. Correction or stabilization of odontoid hypoplasia was found in 64 %. However thoracolumbar kyphosis, scoliosis, hip dysplasia and genua valga were progressive despite HSCT. At the last follow up, 47 % of patients were partially wheelchair dependent, 10 % wheelchair bound and 25 % regularly experienced pain in the spine, hips and lower extremities due to orthopedic problems., Conclusion: Joint mobility, odontoid hypoplasia and craniocervical stenosis might stabilize or even improve in Hurler patients following HSCT. However, despite the beneficial effects on some musculoskeletal manifestations, skeletal complications are frequently observed and the overall burden of orthopedic disease is significant. Frequent multi-disciplinary follow-up in a specialized center are essential. Novel therapeutic approaches (e.g. anti-inflammatory drugs) are needed to improve musculoskeletal outcomes.

One common complication of mucopolysaccharidosis I-Hurler (MPS1-H) is corneal clouding, which occurs despite current treatments, including bone marrow transplantation. Human corneas were obtained from a 14 year old subject with MPS1-H and visual disability from progressive corneal clouding despite a prior bone marrow transplant at age 2. This was compared to a cornea from a 17 year old donated to our eye bank after his accidental death. The corneas were analyzed microscopically after staining with Alcian blue, antibodies to collagen I, IV, VI, and α-smooth muscle actin. Differences in levels of expression of the indicated molecules were assessed. Corneas from Hurler and control mice were examined similarly to determine potential mechanistic overlap. The MPS1-H subject cornea showed elevations in mucopolysaccharide deposition. The MPS1-H and Hurler mice corneas showed increased and disorganized expression of collagen I and IV relative to the control corneas. The MPS1-H corneas also showed increased and disordered expression of collagen VI. Positive expression of α-smooth muscle actin indicated myofibroblast conversion within the MPS1-H cornea in both the patient and mutant mouse material compared to normal human and control mouse cornea. Increased deposition of collagens and smooth muscle actin correlate with corneal clouding, providing a potential mechanism for corneal clouding despite bone marrow transplantation in MPS1-H patients. It might be possible to prevent or slow the onset of corneal clouding by treating the cornea with drugs known to prevent myofibroblast conversion., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study is to describe the natural history of hip morphology in patients with mucopolysaccharidoses (MPS) I and MPS II., Methodology: This is a retrospective radiographic analysis of 88 hips in 44 children with MPS I and II. Radiographs were examined to determine hip migration, femoral head sphericity, and acetabular dysplasia at different ages throughout childhood. In individual hips, change in morphology and rate of change were analyzed., Results: There was a high rate of hip migration and femoral head dysplasia in both MPS I and MPS II. Progressive migration was seen in three quarters of hips and progressive femoral head deformity in over half of hips. Acetabular dysplasia was variable, ranging from normal to severely dysplastic, but did not change with time. Overall, hips were more dysplastic in MPS I than MPS II., Conclusions: Hip morphology is variable in MPS I and MPS II ranging from almost normal to severely dysplastic. Some hips do not deteriorate with time and thus surgical intervention may not be necessary in all cases. Deterioration is slow allowing time to plan a holistic approach to treatment., Level of Evidence: Level IV-case series.