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Background: Mucopolysaccharidoses (MPS) are rare, inherited disorders associated with enzyme deficiencies that result in glycosaminoglycan (GAG) accumulation in multiple organ systems. Management of MPS is evolving as patients increasingly survive to adulthood and undergo multiple surgeries throughout their lives. As surgeries in these patients are considered to be high risk, this can result in a range of critical clinical situations in adult patients.Results: We discuss strategies to prepare for and manage critical clinical situations in adult patients with MPS, including supporting the multidisciplinary team, preoperative and airway assessments, surgical preparations, and postoperative care. We also present eight critical clinical cases (age range: 21-38 years) from four leading inherited metabolic disease centres in Europe to highlight challenges and practical solutions to optimise the care of adult patients with MPS. Critical clinical situations included surgical procedures, pregnancy and a thrombus in a port-a-cath.Conclusions: Individualised strategies to manage critical clinical situations need to be developed for each patient to compensate for the heterogeneous symptoms that may be present and the potential complications that may occur. These strategies should include input from the wider MDT, and be coordinated by metabolic specialists with expertise in the management of MPS disorders and surgery in adult patients with MPS. [ABSTRACT FROM AUTHOR]

Inclusive education of disabled students has been promoted in European disability policies. However, the transition process from more segregated system is slow. The purpose of this study was to provide an insight about different types of schooling of disabled children affected by a rare disease across Europe and to evaluate their and caregivers' well-being. We analysed data from a cross-sectional study (BURQOL-RD) of persons with rare diseases that cause intellectual and/or physical disability: Prader-Willi syndrome, fragile X syndrome, three types of mucopolysaccharidosis and Duchenne muscular dystrophy. The sample consisted of 359 children aged 6–17 and 269 caregivers from eight European countries. Results showed differences between countries in proportion of students placed in special schools, which are still valid option in countries such as Germany, France or UK. Within the inclusive education modalities, lack of special support for disabled students was observed especially in low-income countries. No association between the type of schooling and quality of life was observed, but the subjective caregivers' burden seems to be higher in special schools. The study shows existent differences in implementation of inclusive education in Europe. More research is needed in the field of rare disease disability and educational needs. [ABSTRACT FROM AUTHOR]

Objectives: To assess the health-related quality of life (HRQOL) of patients with mucopolysaccharidosis (MPS) and their caregivers and to quantify the disease-related costs from a societal perspective.Methods: In the context of a multi-country study of rare diseases (BURQOL-RD project), a cross-sectional survey was performed among MPS patients in seven European countries. Data on demographic characteristics, health resource utilization, informal care, and loss of labor productivity were collected. The EQ-5D, Barthel index (BI), and Zarit burden interview (ZBI) questionnaires were used to assess patients' and their informal caregivers' quality of life, patients' functional ability, and caregivers' burden, respectively.Results: Altogether, 120 patients (children 62 %, females 40 %) and 66 caregivers completed the questionnaire. Patients' mean age was 16.5 years and median age at diagnosis was 3 years. Adult patients' average EQ-5D and EQ VAS scores varied across countries from 0.13 to 0.43 and 30.0 to 62.2, respectively, mean BI was 46.7, and ZBI was 32.7. Mean informal care time was 51.3 h/week. The mean total annual cost per patient (reference year 2012) was €24,520 in Hungary, €25,993 in France, €84,921 in Italy, €94,384 in Spain, and €209,420 in Germany. Costs are also shown to differ between children and adults. Direct costs accounted for most of the costs in all five countries (80, 100, 99, 98, and 93 %, respectively).Conclusions: MPS patients experience substantial loss of HRQOL and their families take a remarkable part in their care. Although utilization of health and social care resources varies significantly across countries, MPS incurs considerable societal costs in all the countries studied. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to describe the natural clinical course, incidence and prevalence of mucopolysaccharidosis type VI ( MPS VI) in Russia, Kazakhstan, and Central and Eastern Europe. Methods Patients ( n = 49) were identified by retrieving the data from eight international centers for MPS VI. Results A large number of patients presented with an attenuated phenotype (33%). Height and genotype were related to the severity of the disease, while no clear trend was observed between height and urinary glycosaminoglycan level. A high prevalence of the p. R152W mutation was observed both in the whole series (42%) as well as in Russian patients (43%). The incidence rate ranged from 0.0363 to 0.64 per 100 000 live births in Poland and Lithuania, respectively. Conclusions The observed high p. R152W carrier frequency in the Lithuanian population may indicate a possible founder effect in this region. The high prevalence of this mutation observed in the whole series, as well as the Slavic origin of the majority of patients homozygous for this mutation, suggest that p. R152W may be of Slavic, not Lithuanian origin. Resettlement of the Polish population after World War II resulted in dilution of the prevalence of carriers in Poland and a very low MPS VI incidence. [ABSTRACT FROM AUTHOR]

An inherited deficiency in β-galactosidase can result in GM1 gangliosidosis, with several phenotypes of generalized or chronic psychomotor deterioration, as well as in Morquio disease type B, a characteristic mucopolysaccharidosis free of neurological symptoms. We performed mutation analyses in 17 juvenile and adult patients from various European regions with a deficiency in β-galactosidase and skeletal abnormalities. Fifteen of these had the Morquio B phenotype and have remained neurologically healthy until now while the two others exhibited psychomotor retardation of juvenile onset. A two-base substitution (851-852TG→CT; W273L) was present in 14 of the 15 Morquio B cases. Even if one excludes alleles from patients with possible common descent, there was a much higher frequency (79%) among those with Morquio B phenotype for the W273L mutation than previously reported in the literature (37%). That the Morquio phenotype is also expressed in heterozygotes for W273L and alleles typically found in GM1 gangliosidosis makes it possible to predict the phenotype and reliably detect heterozygotes. A single French patient had a novel missense point mutation (Q408P) together with a known mutation (T500A) while the mentally retarded patients were both heterozygous for two mutations known in chronic GM1 gangliosidosis together with two novel missense point mutations (Y270D and H281Y) in the vicinity of W273L. Our results confirm the high impact of Trp 273 for the function of β-galactosidase and the expression of the Morquio B phenotype. In addition, a second domain around the amino acids 400–500 may also be of significance. [ABSTRACT FROM AUTHOR]

Background: Mucopolysaccharidosis type VII (Sly syndrome) is an ultra-rare neurometabolic disorder caused by inherited deficiency of the lysosomal enzyme β-glucuronidase. Precise data regarding its epidemiology are scarce, but birth prevalence is estimated to vary from 0.02 to 0.24 per 100,000 live births. The clinical course and disease progression are widely heterogeneous, but most patients have been reported to show signs such as skeletal deformities or cognitive delay. Additionally, detection criteria are not standardized, resulting in delayed diagnosis and treatment., Methods: We present a cohort of 9 patients with mucopolysaccharidosis VII diagnosed in the Iberian Peninsula, either in Spain or Portugal. The diagnostic approach, genetic studies, clinical features, evolution and treatment interventions were reviewed., Results: We found that skeletal deformities, hip dysplasia, hydrops fetalis, hepatosplenomegaly, hernias, coarse features, respiratory issues, and cognitive and growth delay were the most common features identified in the cohort. In general, patients with early diagnostic confirmation who received the appropriate treatment in a timely manner presented a more favorable clinical evolution., Conclusions: This case series report helps to improve understanding of this ultra-rare disease and allows to establish criteria for clinical suspicion or diagnosis, recommendations, and future directions for better management of patients with Sly syndrome., (© 2021. The Author(s).)

Purpose: The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders, characterized by the accumulation of glycosaminoglycans within multiple organ systems including the eye. This study aimed to determine the prevalence of glaucoma in patients with MPS, as well as the characteristics, diagnosis and management of patients with MPS and glaucoma., Methods: A multicentre retrospective case-note review was carried out by ophthalmologists from four tertiary referral centres to identify patients with MPS who had been treated for glaucoma. Clinical ophthalmological data were collected using standardized data collection forms., Results: Fourteen patients were identified (27 eyes) of 294 patients with MPS. The prevalence of glaucoma ranged from 2.1% to 12.5%. The median age at diagnosis of glaucoma was 8 years. Diagnostic evaluation of glaucoma was incomplete in many patients: intraocular pressure was documented in all eyes, but optic disc appearance was only assessed in 67%, central corneal thickness in 26%, visual fields in 19% and iridocorneal angle in 15%., Conclusions: Patients with MPS need regular assessment for possible glaucoma including during childhood. Multiple factors contribute to the challenges of assessment, diagnosis and monitoring of glaucoma in these patients., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)