Natural history of valve disease in patients with mucopolysaccharidosis II and the impact of enzyme replacement therapy.

Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare, X-linked lysosomal storage disease caused by reduced activity of iduronate-2-sulfatase (I2S), with subsequent cellular accumulation of the glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate (DS). DS is a major component of the extracellular matrix of heart valves, which can be affected in MPS II. We investigated the natural history of valve disease in MPS II and the impact of long-term intravenous enzyme replacement therapy (ERT) with recombinant I2S (idursulfase). In total, 604 cardiac examinations were assessed from serial follow-up of 80 male patients (49 neuronopathic). Valve disease was classified according to standard practice from hemodynamic features evident from echocardiography. The natural history group comprised 48 patients (up to 14.8 years of follow-up; median, 2.6 years; 24 patients started ERT during the study); 56 patients were treated (up to 14.2 years of follow-up; median, 6.2 years). Lifetime GAG burden (calculated from urinary GAG measurements) correlated significantly with the degree of valve disease. Onset of moderate-to-severe valve disease was significantly delayed in treated (median age at onset, 29.1 ± 2 [95% CI: 25.2-32.9] years; Kaplan-Meier estimation) versus untreated patients (17.6 ± 1 [95% Cl: 15.8-19.4] years; p < 0.0001). Cox regression modeling found that long-term ERT reduced the probability of developing severe valve disease (χ2, 32.736; significant after 5 years of ERT). Overall, this study found that valve disease severity in MPS II correlates with GAG burden and that progression is delayed by long-term ERT.

Left atrial strain correlates with severity of cardiac involvement in Anderson-Fabry disease.

OBJECTIVES: Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD. METHODS: Patients (n = 58, age 40 (29-51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sex-matched healthy controls (HC, n = 58, age 41 [26-56] years, 31 female). RESULTS: A total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain (AUC 0.88, sensitivity 89%, specificity 75%) over the LV strain (AUC 0.82). CONCLUSIONS: LA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications. KEY POINTS: • Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease. • Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain. • Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.

A single center experience in 90 cases with nonimmune hydrops fetalis: diagnostic categories ‒ mostly aneuploidy and still often idiopathic.

OBJECTIVES: The prognosis of nonimmune hydrops fetalis (NIHF) is still poor with a high mortality and morbidity rate despite progress in perinatal care. This study was designed to investigate etiology and outcome of NIHF. METHODS: A retrospective review of 90 NIHF cases from 2007 to 2019 was conducted at University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Demographics, genetic results, prenatal and postnatal outcomes including one year survival as well as autopsy data were extracted. Etiology of hydrops was classified using 13 previously established categories. In 4 patients observed between 2016 and 2019, we used a next-generation-sequencing (NGS) panel for genetic evaluation. RESULTS: Ninety NIHF cases were identified, with a median gestational age (GA) at diagnosis of 14 weeks. There were 25 live-born infants with a median GA of 34 weeks at birth, 15 patients survived to one year. There was aneuploidy in more than one third of the cases. All 90 cases were subclassified into etiologic categories with chromosomal 35, idiopathic 15, syndromic 11, cardiovascular 9, inborn errors of metabolism 6, lymphatic dysplasia 3, thoracic 3, infections 3, gastrointestinal 3 and hematologic 2. The NGS panel was used in 4 cases and 4 diagnoses were made. CONCLUSIONS: In 90 cases with NIHF we identified an aneuploidy in more than one third of the cases. Improved techniques, such as possibly specific genetic analysis, could reduce the high rate of unexplained cases of NIHF.

Diagnosis and Care of Infants and Children with Pompe Disease.

Pompe disease is a rare metabolic myopathy caused by deficiency of lysosomal α-glucosidase. Reduced enzyme activity results in abnormal intra- and extralysosomal glycogen deposition as well as impaired cellular function and autophagy. Age at manifestation and severity of disease depend on residual enzyme activity. Enzyme replacement therapy (ERT) is available since 2006. In infantile onset Pompe disease, the most severe form, markedly prolonged survival has resulted in a new phenotype with symptoms and problems not encountered previously. In addition, it became apparent that antibody formation against the recombinant human enzyme may adversely affect the response to ERT. This review summarizes new knowledge gained in the last years concerning care of pediatric patients with Pompe disease and gives recommendations for diagnostics, treatment, and follow-up.

Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study.

BACKGROUND: Initiation of enzyme replacement therapy (ERT) early in the Fabry disease course may facilitate better outcomes than in patients with advanced disease. Early diagnosis is often hindered by the heterogeneous nature of signs and symptoms, and by the presentation of atypical phenotypes. METHODS: The Sophisticated Assessment of Disease Burden in Patients with Fabry Disease study (SOPHIA; ClinicalTrials.gov, NCT01210196) evaluated clinical and diagnostic assessments for early detection of Fabry-related organ pathology in ERT-naïve patients with mild FD symptoms. Assessments included cardiac magnetic resonance imaging with late gadolinium enhancement (LGE-CMR), echocardiography, 24-h Holter electrocardiography, and biomarkers of FD and fibrosis. RESULTS: 35 patients with mean (SD) baseline age of 45.0 (10.2) years were included and assessed at baseline, 12 months, and (optionally) at 24 months. At baseline, LGE-CMR and elevated procollagen III N-terminal propeptide, sphingosine-1-phosphate, and globotriaosylsphingosine were the most prevalent indicators of early Fabry-related pathology. LGE was already present in 58.8% of patients with normal left ventricular mass index. 15.2% of patients showed grade 1 diastolic dysfunction. QRS duration increased from baseline to last observation, particularly in patients with severe baseline fibrosis. Fibrosis progressed from baseline to last observation, especially in patients with baseline LGE ≥ 2.50 mL (3.65 [1.14] mL vs 6.74 [1.10] mL). Statistically significant correlations were found between LGE volume and high-sensitivity troponin T, and between LGE volume and fragments of urinary collagen alpha-1 (I), (III), and (VII), and collagen alpha-3 (V). CONCLUSIONS: Fibrosis may become apparent before left ventricular hypertrophy occurs. LGE-CMR imaging is superior to conventional echocardiography for detecting early cardiomyopathy in FD and, in conjunction with biomarker tests, may help detect early organ involvement in mild FD.

Differences in myocardial strain between pectus excavatum patients and healthy subjects assessed by cardiac MRI: a pilot study.

OBJECTIVES: To evaluate differences in myocardial strain between pectus excavatum (PE) patients and healthy subjects (HS) assessed by cardiac MRI using the feature-tracking algorithm. METHODS: Cardiac MRI was performed in 14 PE patients and 14 HS (9:5 male to female in each group; age 11-30 years) using a 3T scanner. Post-examination analysis included manual biventricular contouring with volumetry and ejection fraction measurement by two independent radiologists. Dedicated software was used for automated strain assessment. RESULTS: In five of the PE patients, the right ventricular ejection fraction was slightly impaired (40-44 %). PE patients had a significantly higher left ventricular longitudinal strain (P=0.004), mid (P=0.035) and apical (P=0.001) circumferential strain as well as apical circumferential strain rate (P=0.001), mid right ventricular circumferential strain (P=0.008) and strain rate (P=0.035), and apical right ventricular circumferential strain (P=0.012) and strain rate (P=0.044) than HS. The right ventricular longitudinal strain and strain rate did not differ significantly between PE patients and HS. CONCLUSIONS: Myocardial strain differs significantly between PE patients and HS. Higher myocardial strain in the mid and apical ventricles of PE patients indicates a compensation mechanism to enhance ventricular output against basal sternal compression. KEY POINTS: • The right ventricle is frequently affected by the pectus excavatum deformity. • Cardiac MRI revealed differences in myocardial strain in pectus excavatum patients. • Pectus excavatum patients exhibited higher strain in the mid/apical ventricles. • A compensation mechanism to enhance ventricular output against sternal compression is possible.

Evaluating enzyme replacement therapies for Anderson-Fabry disease: commentary on a recent report.

Anderson-Fabry disease (AFD) is a rare lysosomal storage disorder. Randomized controlled clinical trials (RCTs) are preferred as the highest category of evidence, but limited availability of robust evidence in rare diseases may necessitate the use of less rigorous evidence. An analysis of cohort studies of enzyme replacement therapies for AFD published in 2017 by El Dib and coworkers made treatment recommendations that contradict previously published findings from RCTs and a systematic Cochrane review. Our commentary outlines concerns regarding selection criteria and statistical methods with their analysis.

Multicenter midterm follow-up results using the gore septal occluder for atrial septal defect closure in pediatric patients.

OBJECTIVES: To assess the safety and efficacy of the Gore Septal Occluder (GSO) used for device-closure of significant secundum-type atrial septal defects (ASD II) focusing on pediatric patients. BACKGROUND: The GSO is a patch-like double disc device. Due to its design, it is assumed to be safe, even when implanted in ASDs with deficient retro-aortic rims. METHODS: Multicenter retrospective analysis of consecutive children and adolescents with a GSO in situ for at least 12 months according to a 1- to 4-year midterm follow-up. RESULTS: Hundred and seventy three pediatric patients were enrolled. At implantation, median age was 6 years (range 0.7-17.9), median body weight and length were 21 kg (6.4-95) and 119 cm (65-193). Median follow-up period was 20 months (range 12-51). ASD anatomy was comprised of single defects in 131 patients (76%), multi-fenestrated defects in 42 (24%), and deficient retro-aortic rims in 33 (19%). Follow-up confirmed an overall closure-rate of 95.4%. Small residual shunts were reported in eight patients (4.6%) without need for any re-intervention. Complications were classified as minor events both during the initial procedure (9 patients, 5.2%) and on follow-up (another 9 patients), including transient AV block II in three patients (1.8%) and four snare-retrievals (2.4%) during the initial procedure. CONCLUSIONS: Periprocedural and midterm follow-up data have shown the GSO to be effective and safe for ASD device closure in children and adolescents. GSO may be considered the first-choice device in deficient retro-aortic rims and multi-fenestrated defects, when covering most of the atrial septum is necessary. © 2016 Wiley Periodicals, Inc.

Interventional VSD-Closure with the Nit-Occlud® Lê VSD-Coil in 110 Patients: Early and Midterm Results of the EUREVECO-Registry.

In August 2010, the Nit-Occlud® Lê (EUREVECO) became available for transcatheter coil occlusion of ventricular septal defects (VSDs). Retrospective European Registry for VSD Closure using the Nit-Occlud® Lê-VSD-Coil; analysis of the feasibility, results, safety and follow-up of VSD-closure over a 3-year period in 18 European centers. In 102 of 111 patients (female 66), successful VSD closure was performed (mean age 8.2 years, mean weight 28.82 kg), 81 perimembranous VSDs (48 with aneurysm), 30 muscular VSDs, mean procedure time was 121.1 min, and mean fluoroscopy time was 26.3 min. Short- and midterm term follow-up was possible in 100/102 patients, there was 1 embolization and 1 explantation after 24 months. Immediate complete closure occurred in 49 of 101 patients (48.5%), trivial residual shunt was present in 51 (50.0%), closure rate was 95% after 6 months and 97% after 1 year. Out of the 102 patients, there were 2 severe complications (1.8%) (1 severe hemolysis, 1 embolization) and 8 moderate/transient (=7.2%) including 1 transient AV block. During a mean follow-up period of 31.3 months (range 24-48) and a total follow-up time of 224.75 patient years, no further problems occurred. VSD closure with the Nit-Occlud® Lê VSD coil is feasible and safe with a minimal risk of severe side effects. The long-term effects and safety require further clinical follow-up studies.

Transcatheter Closure of Atrial Septal Defects using the GORE(®) Septal Occluder in Children Less Than 10 kg of Body Weight.

The GORE(®) Septal Occluder (GSO) is a well-evaluated device for interventional ASD closure with closure rates comparable to the Amplatzer(®) Septal Occluder (ASO), but there are no published reports of its use in small children weighing less than 10 kg. This may be due to the necessity of a large-sized introducing sheath of at least 10 Fr and therefore the assumed risk of complications in vascular access. The GSO is an alternative option for interventional ASD closure in children weighing less than 10 kg. Fourteen infants and children with a median body weight 8900 g (range 6350-9650 g) underwent successful ASD closure using the GSO. The closure was performed under fluoroscopic and transthoracic echocardiographic guidance. Postprocedure, the vessels passed by the occluder and delivery catheter were examined by duplex sonography. The median ASD diameter was 11 mm (5-17 mm), and the median GSO size was 22.5 mm (15-30 mm), whereas the median ASO left disc size that would have been recommended was 25 mm (17-31 mm). All ASDs were successfully closed. During a median follow-up of 1.57 years (range 0.5-4.2), no complications like erosion, embolization, arrhythmias, or vascular injuries occurred. Although using a 10-Fr introducer sheath, no vascular complications were detected. Our data suggest that the small usable size as well as the soft and flexible design of the device allows successful use of the GSO in young children.

International guidelines for the management and treatment of Morquio A syndrome.

Morquio A syndrome (mucopolysaccharidosis IVA) is a lysosomal storage disorder associated with skeletal and joint abnormalities and significant non-skeletal manifestations including respiratory disease, spinal cord compression, cardiac disease, impaired vision, hearing loss, and dental problems. The clinical presentation, onset, severity and progression rate of clinical manifestations of Morquio A syndrome vary widely between patients. Because of the heterogeneous and progressive nature of the disease, the management of patients with Morquio A syndrome is challenging and requires a multidisciplinary approach, involving an array of specialists. The current paper presents international guidelines for the evaluation, treatment and symptom-based management of Morquio A syndrome. These guidelines were developed during two expert meetings by an international panel of specialists in pediatrics, genetics, orthopedics, pulmonology, cardiology, and anesthesia with extensive experience in managing Morquio A syndrome.

Mucopolysaccharidosis VI: cardiac involvement and the impact of enzyme replacement therapy.

OBJECTIVE: To describe cardiac abnormalities in patients with mucopolysaccharidosis (MPS) VI and to evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function. METHODS: Data from electrocardiographic and echocardiographic evaluations were retrospectively collected from patients with MPS VI who are followed up at the Children's Hospital of Mainz. RESULTS: The study included 44 (16 male and 28 female) patients. At baseline, valvular regurgitation (mainly aortic and mitral) and left ventricular (LV) volume overload were present in over half of patients. Other common cardiac manifestations were sinus tachycardia, LV hypertrophy, concentric LV remodelling, and pulmonary hypertension. One patient had left atrial dilation and one had congestive heart failure. Interventricular septal wall thickness and LV posterior wall thickness were above normal in most patients. Twenty five patients had a pre-ERT and at least one follow-up visit after ERT start. Mean follow-up after ERT start was 5.6 (SD 2.3) years. Despite the late onset (mean age 14.6 years) of treatment, ERT appeared to improve or arrest the progression of LV remodelling and LV hypertrophy and suspend the progression of cardiac valve disease. CONCLUSIONS: MPS VI is associated with an array of cardiac manifestations. ERT appears to have some impact on cardiac structure and function when started late in life, but may have better long-term results when started during early infancy.

Air in the insufflation tube may cause fatal embolizations in laparoscopic surgery: an animal study.

BACKGROUND: The aim of this study was to evaluate the risk of an air embolization with the volume of the insufflation tube during induction of laparoscopy. A further objective was to determine the LD50 of air in young piglets. METHODS: End-tidal carbon dioxide pressure ([Formula: see text]), pulmonary arterial pressure (P pa), heart rate (f c), and mean arterial pressure (P a carot) were measured in 17 piglets divided into three groups: group 1 (n = 6), bolus application (CO2 embolization, followed by air embolization, 2 mL/kg each), group 2 (n = 7), continuous air embolization (30 min, 0.2 mL/kg/min), and group 3 (n = 4), continuous CO2 embolization (30 min, 0.4 mL/kg/min). RESULTS: All animals survived CO2 embolism. Air embolization as a bolus (2 mL/kg) or with an accumulated volume of 3.1 mL/kg led to death. Decreases in [Formula: see text] indicated air or massive CO2 embolization only. There was a good correlation between [Formula: see text] and P pa in case of air embolization (r = -0.80, p < 0.0001). In contrast, no dependency was recognized during CO2 embolism (r = -0.17, p = 0.2). CONCLUSIONS: In order to minimize the lethal risk of gas embolization, the insufflation system has to be completely filled with CO2 before connecting to the patient.

The Prevalence of and Predisposing Factors for Late Atrial Arrhythmias after Transcatheter Closure of Secundum Atrial Septal Defects in Children.

BACKGROUND: A 24 h Holter study in children after transcatheter secundum ASD (ASD II) closure was conducted to detect the prevalence of defects and/or device-related late atrial arrhythmias (LAAs). ASD II closure with an Amplatzer septal occluder (ASO) is an established procedure. Little is known about LAAs after device implantation. METHODS: The eligible participants were children who had undergone ASO implantation, with a follow-up of ≥5 years, as well as one pre- and at least one post-procedural Holter ECG. RESULTS: In total, 161 patients (mean age: 6.2 ± 4.3 years), with a mean follow-up of 12.9 ± 3.1 years (range 5-19), were included. A median of four Holter ECGs per patient were available. LAAs occurred before intervention in four patients (2.5%), and it was peri-interventional in four patients (2.5%), sustained in three patients (1.9%), and developed in three patients (1.9%). In patients with pre- and peri-interventional LAAs, the Qp/Qs ratio was higher (6.4 ± 3.9 vs. non-AA: 2.0 ± 1.1 (p = 0.002)) and the IAS/ASO ratio was lower (1.18 ± 0.27 vs. non-AA: 1.7 ± 0.4 (p < 0.001)). The patients with LAAs differed from those without LAAs in their Qp/Qs (6.8 ± 3.5 vs. 2.0 ± 1.3; p < 0.0001) and IAS/ASO ratios (1.14 ± 0.19 vs. 1.73 ± 0.45; p < 0.001). The patients with LAAs had a Qp/Qs ratio ≥2.94:1, and those who developed LAAs had an IAS/ASO ratio <1.15. CONCLUSIONS: LAAs occurred in 1.9% of patients and were sustained in another 1.9% of patients but persisted in those with large shunt defects and large occluders in relation to the atrial septal length. The predisposing factors for LAAs after ASD closure were a high Qp/Qs ratio, pre-existing atrial arrhythmias, and a low IAS/ASO ratio.

Evaluating Cardiac Lateralization by MRI to Simplify Estimation of Cardiopulmonary Impairment in Pectus Excavatum.

BACKGROUND: The severity of pectus excavatum is classified by the Haller Index (HI) and/or Correction Index (CI). These indices measure only the depth of the defect and, therefore, impede a precise estimation of the actual cardiopulmonary impairment. We aimed to evaluate the MRI-derived cardiac lateralization to improve the estimation of cardiopulmonary impairment in Pectus excavatum in connection with the Haller and Correction Indices. METHODS: This retrospective cohort study included a total of 113 patients (mean age = 19.03 ± 7.8) with pectus excavatum, whose diagnosis was verified on cross-sectional MRI images using the HI and CI. For the development of an improved HI and CI index, the patients underwent cardiopulmonary exercise testing to assess the influence of the right ventricle's position on cardiopulmonary impairment. The indexed lateral position of the pulmonary valve was utilized as a surrogate parameter for right ventricle localization. RESULTS: In patients with PE, the heart's lateralization significantly correlated with the severity of pectus excavatum (p ≤ 0.001). When modifying HI and CI for the individual's pulmonary valve position, those indices are present with greater sensitivity and specificity regarding the maximum oxygen-pulse as a pathophysiological correlate of reduced cardiac function (χ2 10.986 and 15.862, respectively). CONCLUSION: The indexed lateral deviation of the pulmonary valve seems to be a valuable cofactor for HI and CI, allowing for an improved description of cardiopulmonary impairment in PE patients.

RETRACTED: Wiesinger et al. An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis. Pharmaceutics 2023, 15, 1565.

The journal retracts the article, An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis [...].

An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis.

Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases associated with reduced life expectancy and a substantial unmet medical need. Immunomodulatory drugs could be a relevant treatment approach for MPS patients, although they are not licensed for this population. Therefore, we aim to provide evidence justifying fast access to innovative individual treatment trials (ITTs) with immunomodulators and a high-quality evaluation of drug effects by implementing a risk-benefit model for MPS. The iterative methodology of our developed decision analysis framework (DAF) consists of the following steps: (i) a comprehensive literature analysis on promising treatment targets and immunomodulators for MPS; (ii) a quantitative risk-benefit assessment (RBA) of selected molecules; and (iii) allocation phenotypic profiles and a quantitative assessment. These steps allow for the personalized use of the model and are in accordance with expert and patient representatives. The following four promising immunomodulators were identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra might be the treatment of choice for patients with neurocognitive involvement. Nevertheless, a RBA should always be completed on an individual basis. Our evidence-based DAF model for ITTs directly addresses the substantial unmet medical need in MPS and characterizes a first approach toward precision medicine with immunomodulatory drugs.

Clinical characteristics of adults with slowly progressing mucopolysaccharidosis VI: a case series.

OBJECTIVE: To assess clinical features and general health status of adult patients with mucopolysaccharidosis (MPS) VI. METHODS: This report includes the clinical history of patients older than 18 years with slowly progressing MPS VI and the retrospective analysis of the outcomes of available data collected between September 2003 and October 2008 at the Center of Pediatric and Adolescent Medicine, University Medical Center, Johannes Gutenberg-University of Mainz, Germany. Variables included were urinary glycosaminoglycan (uGAG) level, mutation analysis, body height, forced vital capacity (FVC), 6-minute walk test, echocardiographic findings, the need for craniocervical decompression surgery, orthopaedic findings and ophthalmological assessments. RESULTS: The analysis included nine patients with MPS VI aged 19-29 years. The median age at diagnosis was 12 (range 6-20) years. At the time of the assessment (median age 25 years), median uGAG was 29 (range 15-149) µg/mg creatinine and median height 152 (range 136-161) cm. All patients had a FVC below standard values, seven showed reduced endurance in the 6-minute-walk test, all had valve changes with valve replacement in three, two underwent craniocervical decompression surgery, two underwent carpal tunnel surgery, five had ear/nose/throat (ENT) interventions, seven had hip pain/dysplasia, seven had corneal clouding and two were visually impaired. CONCLUSIONS: Although patients with slowly progressing MPS VI are a heterogeneous group showing disease manifestations in several organs, they seem to have some typical characteristics in common. Despite the attenuated clinical course, many of these patients show severe morbidity. Therefore, early diagnosis and proper follow-up and treatment are essential.

The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by the accumulation of glycosaminoglycans (GAGs). GAG storage-induced inflammatory processes are a driver of cytopathology in MPS and pharmacological immunomodulation can bring improvements in brain, cartilage and bone pathology in rodent models. This manuscript reviews current knowledge with regard to inflammation in MPS patients and provides hypotheses for the therapeutic use of immunomodulators in MPS. Thus, we aim to set the foundation for a rational repurposing of the discussed molecules to minimize the clinical unmet needs still remaining despite enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT).