Maroteaux-Lamy Research Articles

Brain MRI findings in patients with mucopolysaccharidosis type VI (MPS VI)

Brain MRI findings in patients with mucopolysaccharidosis type VI (MPS VI)

Use of biomarkers to follow up positive lysosomal diseases in newborn screening

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.Data from patients who initiated treatment at < 5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated.A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved.The prescribed dosage of 1 mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population.

Long-term enzyme replacement therapy for MPS VI: 8-year follow up of a Colombian patient

Long-term enzyme replacement therapy for MPS VI: 8-year follow up of a Colombian patient

Cardiac Evaluation using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses.

Background: Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders that can damage various organs, including the heart. Cardiac abnormalities have been observed in patients with all MPS types, with the most documented abnormalities being cardiac valvular regurgitation and stenosis, valvular thickening, and hypertrophic cardiomyopathy. Methods: Cardiac features of 53 Taiwanese patients with MPS (31 men and 22 women; age range 1.1–34.9 years; seven with MPS I, 16 with MPS II, nine with MPS III, 14 with MPS IVA, and seven with MPS VI) were evaluated using two-dimensional speckle-tracking echocardiography and conventional echocardiography. Results: The mean z scores of the global longitudinal strain (GLS), left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter of the 53 patients with MPS were 1.71, 0.35, 1.66, 1.03, and 3.15, respectively. Furthermore, z scores >2 were identified in 45%, 13%, 40%, 13%, and 70% of the GLS, LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most severe GLS was observed in those with MPS VI, followed by in those with MPS II and MPS I. The GLS z score was positively correlated with the LVMI z score (p < 0.01). Moreover, diastolic dysfunction (reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio < 1)) was identified in 12 patients (23%). Ejection and shortening fractions were abnormal in four (8%) and seven (13%) patients, respectively. Mitral regurgitation (MR) (92%) was the most common valvular heart disease, followed by aortic regurgitation (AR) (57%), mitral stenosis (MS) (21%), and aortic stenosis (AS) (15%). The z scores of the GLS and LVMI and severity scores of the MS, MR, AS, and AR were all positively correlated with increasing age (p < 0.05). Twenty patients (38%) had a left ventricular remodeling pattern. Conclusions: The most significant left ventricular myocardial deformation, hypertrophy and valvular heart disease were observed in the patients with MPS VI, II, and I, followed by those with MPS IV; in contrast, patients with MPS III had the mildest manifestations. Cardiac abnormalities in patients with MPS worsened with increasing age in accordance with the progressive nature of this disease.

Molecular Characterization of a Novel Splicing Mutation Underlying Mucopolysaccharidosis (MPS) Type VI—Indirect Proof of Principle on Its Pathogenicity

Here, we present the molecular diagnosis of a patient with a general clinical suspicion of Mucopolysaccharidosis, highlighting the different tools used to perform its molecular characterization. In order to decrease the turnaround time for the final report and contribute to reduce the “diagnostic odyssey”, which frequently afflicts affected families, the proband’s sample was simultaneously screened for mutations in a number of lysosomal function-related genes with targeted next-generation sequencing (NGS) protocol. After variant calling, the most probable cause for disease was a novel ARSB intronic variant, c.1213+5G>T [IVS6+5G>T], detected in homozygosity. In general, homozygous or compound heterozygous mutations in the ARSB gene, underlie MPS type VI or Maroteaux-Lamy syndrome. Still, even though the novel c.1213+5G>T variant was easy to detect by both NGS and Sanger sequencing, only through indirect studies and functional analyses could we present proof of principle on its pathogenicity. Globally, this case reminds us that whenever a novel variant is detected, its pathogenicity must be carefully assessed before a definitive diagnosis is established, while highlighting alternative approaches that may be used to assess its effect in the absence RNA/cDNA sample(s) from the proband. This is particularly relevant for intronic variants such as the one here reported. Special attention will be given to the use of reporter minigene systems, which may be constructed/designed to dissect the effect of this sort of alterations, providing an insight into their consequences over the normal pre-mRNA splicing process of the affected gene.

Clinical and Radiologic Diagnosis of a Patient with Maroteaux-Lamy Syndrome

Background: Diagnosis of rare diseases or disorders is understandably challenging because it is unfeasible for practicing physicians to make themselves familiar with hundreds of rare diseases. The diagnosis of rare inherited metabolic syndromes such as mucopolysaccharidoses is additionally complicated by the lack of confirmatory sophisticated laboratory tests in many areas of the world. In the more developed countries, the diagnosis of mucopolysaccharidoses depends on urine tests for excessive mucopolysaccharides and enzyme assays. However, these tests are not easily accessible in countries like Iraq, and the diagnosis has to rely on clinical and radiological findings. Case Report: The clinical and radiologic diagnosis of an Iraqi patient with Maroteaux-Lamy syndrome is described. The clinical diagnosis of the girl with early-onset mucopolysaccharidosis and the abnormalities were recognizable before the age of two. The clinical and radiologic diagnosis was Maroteaux-Lamy syndrome because of the absence of mental retardation and the presence of hepatosplenomegaly. Conclusion: Clinical diagnosis of rare metabolic syndromes like mucopolysaccharidoses requires magnificent clinical skills and huge experience because of the similarity between various types of mucopolysaccharidoses.

Anterior Chamber Angles in Different Types of Mucopolysaccharidoses

To evaluate the anterior chamber angle status and estimate the intraocular pressure (IOP) in patients with mucopolysaccharidoses (MPSs) type I, II, IV, and VI. Prospective cross-sectional study. This study enrolled 27 consecutive MPS patients (8 patients with MPS I, 4 patients with MPSII, 9 patients with MPS IV, and 6 patients with MPS VI) and 20 normal control subjects. Anterior chamber angle status was evaluated by swept-source optical coherence tomography and IOP was estimated by the new-generation tonometer Corvis ST. Twelve eyes (6 patients) of 15 eyes (8 patients) with MPS I had narrow angles or peripheral iridocorneal touches together with elevated IOP (80%). Six eyes (3 patients) of 8 eyes (4 patients) with MPS II had plateau iris configuration, but all 8 eyes had normal IOP. All 18 eyes (9 patients) with MPS IV had normal angle structures, but 8 eyes (4 patients) had elevated IOP (44.4%). Nine eyes (5 patients) of 11 eyes (6 patients) with MPS VI had shallow but not closed angles (81.8%). Among these 9 eyes, 5 eyes had elevated IOP, and 4 of these 5 eyes had IOP >30mm Hg. The trabecular iris angles of MPS types I, II, and VI were smaller than those of MPS type IV and of the control subjects. The angle recess areas of MPS types I and VI were smaller than those of MPS type IV and of the control subjects. MPS type I patients are prone to have glaucoma with narrow or closed angles; MPS type II patients tend to have plateau iris; MPS type IV patients are vulnerable to open-angle glaucoma; MPS type VI patients have narrow angles not as close as those of MPS type I. MPS types I, IV, and VI had higher IOP estimates than the control subjects, but only MPS I and IV had higher corrected IOP estimates than the control subjects. The ordinary IOP estimates in MPS VI patients may be falsely high because of clouded corneas and increased corneal rigidity. Swept-source optical coherence tomography helps ophthalmologist investigate the angle structure and the pathophysiology of glaucoma caused by MPS.

Clinical and Radiologic Diagnosis of a Patient with Maroteaux-Lamy Syndrome

Clinical and Radiologic Diagnosis of a Patient with Maroteaux-Lamy Syndrome

Laryngeal, Tracheal, and Bronchial Disease in the Mucopolysaccharidoses: Endoscopic Study.

Mucopolysaccharidoses (MPS) are genetically determined diseases, leading to a deficiency of enzymes in the glycosaminoglycan (GAG) degradation pathway. The accumulation of GAG occurs in connective tissue in various organs and systems of the body, including the larynx, trachea, and bronchi. Respiratory symptoms are common and severe in these patients, and respiratory disease is a frequent cause of death. A cross-sectional study with flexible bronchoscopy was conducted in 30 MPS patients (6 MPS I, 8 MPS II, 2 MPS III, 3 MPS IV-A, and 11 MPS VI). Only four patients (13.33%) had a normal airway; nine (30%) had mild to moderate disease, 12 (40%) moderate to severe, and five patients (16.67%) had severe disease. Of particular interest, neuronopathic MPS II had the largest proportion of tracheostomized patients who died due to respiratory complications; in MPS IV-A, all patients had significant tracheobronchial deformity with associated tracheomalacia, despite lacking laryngeal involvement. Laryngotracheobronchial disease (LTBD) was associated to longer disease history and was significantly more severe in older patients. Longer use of enzyme replacement therapy did not prevent the progression of LTBD, although the age of therapy introduction may be a crucial factor in lower airway involvement.

Implementation of an Affordable Method for MPS Diagnosis from Urine Screening to Enzymatic Confirmation: Results of a Pilot Study in Morocco.

Rapid and accurate diagnosis of mucopolysaccharidoses (MPS) is still a challenge due to poor access to screening and diagnostic methods and to their extensive clinical heterogeneity. The aim of this work is to perform laboratory biochemical testing for confirming the diagnosis of mucopolysaccharidosis (MPS) for the first time in Morocco. Over a period of twelve months, 88 patients suspected of having Mucopolysaccharidosis (MPS) were referred to our laboratory. Quantitative and qualitative urine glycosaminoglycan (GAG) analyses were performed, and enzyme activity was assayed on dried blood spots (DBS) using fluorogenic substrates. Enzyme activity was measured as normal, low, or undetectable. Of the 88 patients studied, 26 were confirmed to have MPS; 19 MPS I (Hurler syndrome; OMIM #607014/Hurler-Scheie syndrome; OMIM #607015), 2 MPS II (Hunter syndrome; OMIM #309900), 2 MPS IIIA (Sanfilippo syndrome; OMIM #252900), 1 MPS IIIB (Sanfilippo syndrome; OMIM #252920) and 2 MPS VI (Maroteaux-Lamy syndrome; OMIM #253200). Parental consanguinity was present in 80.76% of cases. Qualitative urinary glycosaminoglycan (uGAGs) assays showed abnormal profiles in 31 cases, and further quantitative urinary GAG evaluation and Thin Layer Chromatography (TLC) provided important additional information about the likely MPS diagnosis. The final diagnosis was confirmed by specific enzyme activity analysis in the DBS samples. The present study shows that the adoption of combined urinary substrate analysis and enzyme assays using dried blood spots can facilitate such diagnosis, offer an important tool for an appropriate supporting care, and a specific therapy, when available.

Newborn screening for lysosomal disorders in Brazil: A pilot study using customized fluorimetric assays.

Lysosomal storage disorders (LSDs) are a group of genetic disorders characterized by deficiency of specific lysosomal enzymes. In general, patients are clinically normal at birth, and progressively develop severe signs and symptoms. Diagnosis is usually made several years after onset of manifestations, preventing patients to have the benefits of the early treatment. Newborn screening programs are being considered for LSDs to allow early diagnosis and treatment. The present study evaluated the feasibility of a customized screening approach based on modified fluorometric assays with reduced amounts of reagents, substrates and samples for: mucopolysaccharidosis (MPS) type I (MPS I), MPS VI, Fabry, Gaucher, and Pompe diseases. We also evaluated the advantages of including blood chitotriosidase and urinary glycosaminoglycans in the protocol. By the measurement of the specific disease-associated enzymes (plus blood chitotriosidase and urinary glycosaminoglycans) we analyzed 834 de-identified DBS of unselected newborns. No positive case was detected, and the false-positive rates were low. Taking into consideration the limitations of this methodology, we believe that, after defining proper cutoffs, it could be a viable alternative to provide NBS for LSDs by laboratories that may not be able to afford the commercial methods available.

Perthes-Like Disease Masquerading Non-Classical MPS

Abstract Mucopolysaccharidoses (MPS) are inborn errors of metabolism caused by deficient lysosomal enzymes, leading to organomegaly, hip osteonecrosis, coarse facial features, bone deformities, joint stiffness, cardiac and pulmonary symptoms (MPS VI) or hypermobility (MPS IVA). Some patients may present with non-classical forms of the disease in which osteoarticular abnormalities are the initial symptoms of non-classical forms. As orthopedists and surgeons are the specialists most frequently consulted before the diagnosis, it is critical that MPS may be considered as a differential diagnosis for patients with bone dysplasia. Experts in Latin America reviewed medical records focusing on disease onset, first symptoms and the follow-up clinical and surgical outcomes of non-classical MPS VI and IVA patients. All patients displayed orthopedic issues, which worsened over time, followed by cardiac and ophthalmological abnormalities. Our findings enlighten the necessity of including non-classical MPS as possible diagnosis for patients who report osteoarticular abnormalities in absence of inflammation.

Fundoscopic Changes in Maroteaux-Lamy Syndrome

Purpose To describe a clinical case of mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, with fundoscopic alterations that may correspond to scleral deposits of glycosaminoglycans. Materials and Methods Clinical case report. Results A 16-year-old girl with MPS VI was examined at the Ophthalmology Department for poor vision due to opacified corneas. Treatment consisted of bilateral penetrating keratoplasty. Retinographies and enhanced depth imaging optical coherence tomography (EDI-OCT) were performed after surgery, suggesting the presence of scleral glycosaminoglycan deposits. The patient evolved with stable corneal and fundoscopic findings. Conclusions To our knowledge, this is the first case of MPS VI described in vivo with suspected deposits of glycosaminoglycans in the sclera. Fundoscopic alterations are not usually included in the ocular pathological spectrum of MPS VI. However, with improved control of systemic comorbidities, survival rates of these patients have increased, which in turn has made it possible to observe other changes besides the ones that were classically described. Despite being particularly challenging to manage, efforts should be made to maximizing the visual acuity of these patients, in order to provide them the best possible quality of life.

Relationships among Height, Weight, Body Mass Index, and Age in Taiwanese Children with Different Types of Mucopolysaccharidoses.

Background: Children with mucopolysaccharidosis (MPS) generally appear unaffected at birth but may develop multiple clinical manifestations including profound growth impairment as they grow older. Each type of MPS has a variable age at onset and variable rate of progression, however, information regarding growth in Asian children is limited. Methods: This retrospective analysis included 129 Taiwanese patients with MPS (age range, 0.7 to 19.5 years, median age, 7.9 years) from eight medical centers in Taiwan from January 1996 through December 2018. Results: The mean z scores for the first recorded values of height, weight, and body mass index in the patients’ medical records were −4.25, −1.04, and 0.41 for MPS I (n = 9), −2.31, 0.19, and 0.84 for MPS II (n = 49), −0.42, 0.08, and −0.12 for MPS III (n = 27), −6.02, −2.04, and 0.12 for MPS IVA (n = 30), and −4.46, −1.52, and 0.19 for MPS VI (n = 14), respectively. MPS IVA had the lowest mean z scores for both height and weight among all types of MPS, followed by MPS VI, MPS I, MPS II, and MPS III, which showed the mildest growth retardation. Both z scores for height and weight were negatively correlated with increasing age for all types of MPS (p < 0.01). Of 32 patients younger than 5 years of age, 16 (50%), and 23 (72%) had positive z scores of height and weight, respectively. A substantial number of younger patients with MPS I, II, III, and IVA had a positive height z score. The median age at diagnosis was 3.9 years (n = 115). Conclusions: The patients with MPS IVA had the most significant growth retardation among all types of MPS, followed by MPS VI, MPS I, MPS II, and MPS III. The height and weight of the MPS patients younger than 2–5 years of age were higher than those of healthy individuals, however, their growth significantly decelerated in subsequent years. Understanding the growth curve and potential involved in each type of MPS may allow for early diagnosis and timely management of the disease, which may improve the quality of life.

Free urinary glycosylated hydroxylysine as an indicator of altered collagen degradation in the mucopolysaccharidoses.

Extracellular matrix (ECM) disruption is known to be an early pathological feature of the Mucopolysaccharidoses (MPS). Collagen is the main component of the ECM and its metabolism could act as a useful indicator of ECM disruption. We have measured the specific collagen breakdown products; urinary free hydroxylated (Lys-OH) and glycosylated hydroxylysines (Lys-O-Gal and Lys-O-GalGlc) in MPS patients using a tandem liquid chromatography tandem mass spectrometry assay. A pilot study cohort analysis indicated that concentrations of lysine and Lys-OH were raised significantly in MPS I (Hurler) disease patients. Lys-O-GalGlc was raised in MPS II and MPS VI patients and demonstrated a significant difference between MPS I Hurler and an MPS I Hurler-Scheie group. Further analysis determined an age association for glycosylated hydroxylysine in control samples similar to that observed for the glycosaminoglycans. Using defined age ranges and treatment naïve patient samples we confirmed an increase in glycosylated hydroxylysines in MPS I and in adult MPS IVA. We also looked at the ratio of Lys-O-Gal to Lys-O-GalGlc, an indicator of the source of collagen degradation, and noticed a significant change in the ratio for all pediatric MPS I, II, and IV patients, and a small significant increase in adult MPS IV. This indicated that the collagen degradation products were coming from a source other than bone such as cartilage or connective tissue. To see how specific the changes in glycosylated hydroxylysine were to MPS patients we also looked at levels in patients with other inherited metabolic disorders. MPS patients showed a trend towards increased glycosylated hydroxylysines and an elevated ratio compared to other metabolic disorders that included Battens disease, Fabry disease, Pyridoxine-dependent epilepsy (due to mutations in ALDH7A1), and Niemann Pick C disease.

A Novel Pathological ARSB Mutation (c.870G>A; p.Trp290stop) in Mucopolysaccharidosis Type VI Patients

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder, characterized by the deficiency of the arylsulfatase B enzyme. The clinical phenotype and severity of the illness varies according to the residual enzyme activity. Typical features are a short stature, shortened trunk, protuberant abdomen, flexed-knee stance, arched back, corneal clouding, joint stiffness and contractures as well as a waddling gait. Patients typically have Hurler-like dysmorphic facial features: microcephaly, prominent forehead and eyes, a broad nose, low nasal bridge, thick lips, and hyperplastic gums with widely spaced teeth. Complications of the illness include obstructive airway, cardiac valvular problems, splenomegaly, hernias, and pneumonia. Unlike other MPS diseases, MPS VI is characterized by normal intellectual development. Since the disease is due to deficient glycosaminoglycan (mucopolysaccharide) metabolism, elevated urinary glycosaminoglycan levels are a main indicator of MPS. Diagnosis is confirmed by enzyme assays, specifically low arylsulfatase B activity in conjunction with the normal activity of other lysosomal enzymes. Enzyme replacement therapy and hematopoietic stem cell therapy are showing positive results in the management of the condition. The more severely affected patients, with a rapidly advancing form of the disease, have a short life span and succumb, most commonly to heart failure, by early adulthood. The frequency of ARSB variants in patients with MPS VI are as follows: 59.5% missense, 13.5% small deletions, 12% nonsense, 5% splice site or intronic variants, 3% small duplications, 3% large deletions, and 1% stop-loss. We report an Albanian family with siblings diagnosed with MPS Vl after clinical examination, biochemical tests, and molecular analysis. Hereby, a novel c.870G>A nonsense homozygous mutation was found responsible for the loss of the enzyme activity.

Enzyme replacement therapy for mucopolysaccharidoses; past, present, and future.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders, which lack an enzyme corresponding to the specific type of MPS. Enzyme replacement therapy (ERT) has been the standard therapeutic option for some types of MPS because of the ability to start immediate treatment with feasibility and safety and to improve prognosis. There are several disadvantages for current ERT, such as limited impact to the brain and avascular cartilage, weekly or biweekly infusions lasting 4-5 h, the immune response against the infused enzyme, a short half-life, and the high cost. Clinical studies of ERT have shown limited efficacy in preventing or resolving progression in neurological, cardiovascular, and skeletal diseases. One focus is to penetrate the avascular cartilage area to at least stabilize, if not reverse, musculoskeletal diseases. Although early intervention in some types of MPS has shown improvements in the severity of skeletal dysplasia and stunted growth, this limits the desired effect of ameliorating musculoskeletal disease progression to young MPS patients. Novel ERT strategies are under development to reach the brain: (1) utilizing a fusion protein with monoclonal antibody to target a receptor on the BBB, (2) using a protein complex from plant lectin, glycan, or insulin-like growth factor 2, and (3) direct infusion across the BBB. As for MPS IVA and VI, bone-targeting ERT will be an alternative to improve therapeutic efficacy in bone and cartilage. This review summarizes the effect and limitations on current ERT for MPS and describes the new technology to overcome the obstacles of conventional ERT.

Human medicines European public assessment report (EPAR): Naglazyme, galsulfase, Mucopolysaccharidosis VI, Date of authorisation: 23/01/2006, Revision: 14, Status: Authorised

Human medicines European public assessment report (EPAR): Naglazyme, galsulfase, Mucopolysaccharidosis VI, Date of authorisation: 23/01/2006, Revision: 14, Status: Authorised

Enzyme replacement therapy initiated in adulthood: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program

ObjectiveTo evaluate the impact of galsulfase enzyme replacement therapy (ERT) when initiated in adulthood for patients with mucopolysaccharidosis (MPS) VI. MethodsIn 2005, the multi-national, MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A sub-analysis was performed in patients who started ERT at ≥16 years of age and had received galsulfase for ≥6 months. Urinary glycosaminoglycans (uGAG), 6-min walk test (6MWT), 3-min stair climb test (3MSCT), pulmonary function measures, cardiac function, ophthalmology measures, liver and spleen sizes, and safety were evaluated. ResultsOf 223 patients enrolled in the CSP, 51 were included in the sub-analysis. Patients were between 16 and 63 years of age at first infusion. From pre-treatment baseline, uGAG level decreased by a mean (±standard deviation [SD]) of 66 (±45)% (N = 29) after a median follow-up of 7.2 years. 6MWT distance decreased slightly by a mean of 17 (±107) meters (N = 23) after 6.6 years. Stairs/min in the 3MSCT increased by a mean of 26 (±33) (N = 14) after 2.8 years. Pulmonary function measures, forced expiratory volume in 1 second and forced vital capacity, increased by a mean of 0.06 (±0.21) L after 7.3 years and 0.05 (±0.28) L after 7.2 years, respectively (N = 19 for both measures). Overall, galsulfase was well tolerated, with most adverse events reported being MPS-related clinical manifestations and not related to galsulfase. ConclusionsResults of this sub-analysis of the CSP suggest that initiation of galsulfase in adulthood is well tolerated and can possibly stabilize MPS VI in the long term.

Functional independence of Taiwanese patients with mucopolysaccharidoses.

BackgroundInformation on functional strengths and weaknesses of mucopolysaccharidosis (MPS) patients is important for early intervention programs and enzyme replacement therapy (ERT).MethodsWe used the Functional Independence Measure for Children (WeeFIM) questionnaire to assess the functional skills of 63 Taiwanese MPS patients (median age, 13 years 3 months; range, 3–20 years) from January 2012 to December 2018.ResultsMean total WeeFIM score was 75.4 of a potential score of 126. Mean total WeeFIM scores of each type (MPS I, MPS II, MPS IIIB, MPS IVA, and MPS VI) were 103.8, 76.2, 41.6, 92.2, and 113.6, respectively. Mean scores for self‐care, mobility, and cognition domains were 30 (maximum 56), 23 (maximum 35), and 22 (maximum 35), respectively. MPS type IIIB patients had the lowest scores in self‐care, mobility, cognition, and total domains compared to other types of MPS. All patients with ERT in MPS I, II, and IVA had higher scores in self‐care and mobility domains than patients without ERT. Most patients required assistance for self‐care skills, especially in grooming and bathing.ConclusionMPS patients require support and supervision in self‐care tasks. For cognition tasks, MPS IIIB patients also require help. This questionnaire is useful to identify the strengths and limitations of MPS patients.