The outcomes of alpha-mannosidosis after hematopoietic stem cell transplantation (HSCT) are incompletely described. This retrospective multi-center study evaluated the outcomes of patients who underwent HSCT for their alpha-mannosidosis after 2010. Twenty-one children (11 females) with enzymatically and/or genetically confirmed alpha-mannosidosis, diagnosed at a mean age of 14 months (0-60 months), were included. The median age at HSCT was 3.9 years (10 months to 13.3 years) with a median follow-up of 2.3 years (0.3-14.1 years). Seventy-four percent (14/19) of patients received an unrelated graft while the rest had a matched sibling donor. Primary engraftment was reached in 17 of 21 patients; four patients required a second HSCT with successful subsequent engraftment. Nine patients had severe post-HSCT infections, five patients developed acute graft-versus-host disease (GvHD) (> = grade II), and one patient had chronic GvHD. No patient died during follow-up. Seven out of ten patients received enzyme replacement therapy both pre- and post-HSCT. Among children with clinical symptoms, improvement was documented in hepatomegaly (40% of patients before HSCT, down to 10% after), recurrent infections (62%/30%), and hearing disorder (85%/65%). In 13 patients with developmental data, outcomes after HSCT suggested at least mild delays persisted post-HSCT in the majority (85%), with some trends of higher functioning with earlier treatment. Findings suggest HSCT has shown notable improvements in safety and is associated with clinical benefit in alpha-mannosidosis. Neurodevelopmental findings require longer-term study to account for phenotypic diversity.
- MeSH
- alfa-mannosidóza * terapie diagnóza komplikace MeSH
- dítě MeSH
- enzymová substituční terapie MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- následné studie MeSH
- nemoc štěpu proti hostiteli etiologie MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky metody MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Alpha-mannosidosis is a rare recessive lysosomal storage disorder with progressive multi-systemic impacts. In the absence of standardized monitoring protocols, there is insufficient understanding of disease progression over time. This study explored the evolution of the burden of illness and quality of life (QoL) experienced by patients with alpha-mannosidosis via an international patient and caregiver-based survey. The online survey was distributed to adult patients/caregivers of patients ≥ 10 years old. It included visual analogue scales (VAS; timepoints 5 years ago and now), multiple choice, and open text questions. We report a subset of functional and QoL data: walking ability, pain/discomfort, ability to self-care, and mental health. RESULTS: Analyses include 51 responses from 18 countries: 26 patients were on velmanase alfa enzyme replacement therapy (ERT), seven had been treated with hematopoietic stem cell transplantation (HSCT) and 18 were untreated patients (UP). Over 5 years, VAS scores showed the least decline in walking ability for HSCT patients (+ 0.1 ± 1.9) compared to patients receiving ERT (+ 0.7 ± 1.2) and UP (+ 1.8 ± 2.0). A trend towards improvement in pain was only observed for those on ERT (-0.2 ± 2.0), both for pediatric and adult patients. Ability to self-care improved for patients treated with HSCT (-1.0 ± 1.8) and slightly improved with ERT (-0.3 ± 1.5) but worsened for UP (+ 0.6 ± 0.9). Similarly, a trend towards improvement in mental health scores was observed for patients on ERT (-0.4 ± 2.2). CONCLUSIONS: Alpha-mannosidosis is associated with a substantial and progressive burden in UP, including deterioration in walking ability, pain, self-care and mental health. The survey results suggest that treatment with ERT or HSCT may slow this natural progression of alpha-mannosidosis, with these patients following a different disease trajectory to those solely receiving supportive care. This study could inform the natural pathway of alpha-mannosidosis to recognize patients' needs, courses of care, and the design of interventional studies.
- MeSH
- alfa-mannosidóza * patofyziologie terapie MeSH
- bolest * patofyziologie MeSH
- dospělí MeSH
- duševní zdraví MeSH
- enzymová substituční terapie MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- osoby pečující o pacienty MeSH
- péče o sebe MeSH
- průzkumy a dotazníky MeSH
- transplantace hematopoetických kmenových buněk MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Hearing impairment is a prevalent clinical feature in Morquio syndrome (mucopolysaccharidosis IVA or MPS IVA) patients, often presenting in diverse forms: conductive, sensorineural, or a combination known as mixed hearing loss. The mixed form entails a blend of both conductive and sensorineural elements, typically exhibiting a progressive trajectory. This scoping review aimed to comprehensively analyze available evidence pertaining to the pathophysiology, classification, epidemiology, and clinical management of hearing loss in individuals with MPS IVA. METHODS: Targeted literature was searched using MEDLINE, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Web of Science, the Cochrane Library, Trip Medical Database, Embase, ScienceDirect, and Google Scholar, with a second search cycle to identify gray literature. A systematic search strategy using Medical Subject Headings keywords was implemented: "Hearing Disorders" OR "Hearing Loss" AND "Mucopolysaccharidosis IV" or "Hearing Disorders" OR "Hearing Loss" AND "Mucopolysaccharidosis IV." The identified bibliography was uploaded to COVIDENCE platform for information management. Articles were screened by 3 independent reviewers following the eligibility criteria. RESULTS: Twenty-seven articles met the inclusion criteria, spanning information from 568 patients across 16 different countries. None of the studies had complete epidemiological information. Only 2 studies provided sufficient data to address the pathophysiology, while 3 addressed management and treatment. Hearing loss was reported in 210 of 568 patients. A total of 19.2% of patients reported recurrent ear infections. None of the studies reported vertigo, tinnitus, or dizziness in the patients. Pure-tone audiometry was the primary test used to diagnose and monitor auditory impairment in patients with Morquio syndrome. CONCLUSIONS: Five hundred sixty-eight patients with MPS IVA were identified, of whom 210 (37%) developed hearing loss, the most common of which was moderate. Despite the lack of information on the diagnosis and management of hearing loss in Morquio syndrome, this study found that approximately one-third of participants exhibited some form of auditory impairment, with the majority of these cases being sensorineural in nature.
- MeSH
- lidé MeSH
- mukopolysacharidóza IV * komplikace epidemiologie diagnóza MeSH
- nedoslýchavost * epidemiologie diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- scoping review MeSH
Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.
- Klíčová slova
- brodalumab,
- MeSH
- biologická terapie metody MeSH
- dospělí MeSH
- hidradenitis suppurativa * farmakoterapie komplikace patologie MeSH
- komorbidita MeSH
- lidé MeSH
- mukopolysacharidóza IV * komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
Despite the adenoids are regularly removed in patients with mucopolysaccharidoses (MPS), the underlying tissue and cellular pathologies remain understudied. We characterized an (immuno)histopathologic and ultrastructural phenotype dominated by lysosomal storage changes in a specific subset of adenotonsillar paracortical cells in 8 MPS patients (3 MPS I, 3 MPS II, and 2 MPS IIIA). These abnormal cells were effectively detected by an antibody targeting the lysosomal membrane tetraspanin CD63. Important, CD63+ storage vacuoles in these cells lacked the monocytes/macrophages lysosomal marker CD68. Such a distinct patterning of CD63 and CD68 was not present in a patient with infantile neurovisceral variant of acid sphingomyelinase deficiency. The CD63+ storage pathology was absent in two MPS I patients who either received enzyme-replacement therapy or underwent hematopoietic stem cells transplantation prior the adenoidectomy. Our study demonstrates novel features of lysosomal storage patterning and suggests diagnostic utility of CD63 detection in adenotonsillar lymphoid tissue of MPS patients.
- MeSH
- antigeny CD63 MeSH
- enzymová substituční terapie MeSH
- lidé MeSH
- lymfoidní tkáň patologie MeSH
- lyzozomy MeSH
- mukopolysacharidózy * diagnóza farmakoterapie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Current literature lacks consensus on initial assessments and routine follow-up care of patients with alpha-mannosidosis (AM). A Delphi panel was conducted to generate and validate recommendations on best practices for initial assessment, routine follow-up care, and integrated care coordination of patients with AM. METHODS: A modified Delphi method involving 3 rounds of online surveys was used. An independent administrator and 2 nonvoting physician co-chairs managed survey development, anonymous data collection, and analysis. A multidisciplinary panel comprising 20 physicians from 12 countries responded to 57 open-ended questions in the first survey. Round 2 consisted of 11 ranking questions and 44 voting statements. In round 3, panelists voted to validate 60 consensus statements. The panel response rate was ≥95% in all 3 rounds. Panelists used 5-point Likert scales to indicate importance (score of ≥3) or agreement (score of ≥4). Consensus was defined a priori as ≥75% agreement with ≥75% of panelists voting. RESULTS: Consensus was reached on 60 statements, encompassing 3 key areas: initial assessments, routine follow-up care, and treatment-related follow-up. The panel agreed on the type and frequency of assessments related to genetic testing, baseline evaluations, quality of life, biochemical measures, affected body systems, treatment received, and integrated care coordination in patients with AM. Forty-nine statements reached 90% to 100% consensus, 8 statements reached 80% to 85% consensus, and 1 statement reached 75% consensus. Two statements each reached consensus on 15 baseline assessments to be conducted at the initial follow-up visit after diagnosis in pediatric and adult patients. CONCLUSION: This is the first Delphi study providing internationally applicable, best-practice recommendations for monitoring patients with AM that may improve their care and well-being.
- MeSH
- alfa-mannosidóza * terapie diagnóza MeSH
- delfská metoda * MeSH
- integrované poskytování zdravotní péče normy MeSH
- konsensus * MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Lysosomální střádavá onemocnění (iysosomai storage diseases, LSD) jsou skupinou více než 70 onemocnění, jejichž nejčastější příčinou je nedostatečná aktivita některého z hydrolytických enzymů. Tento přehledový článek ilustruje aktuální terapeutické možnosti LSD. Jedná se o enzymovou substituční terapii, substrát redukující terapii, terapii chaperony a transplantaci hematopoetických kmenových buněk. Mezi další slibné strategie vyvinuté v posledních letech patří genová terapie nebo genová terapie hematopoetických kmenových buněk. U všech z uvedených terapií platí zlaté pravidlo, že k dosažení dobrého účinku léčby je zásadní časná diagnostika onemocnění a zahájení léčby.
Lysosomal storage diseases (LSD) are a group of more than 70 diseases, the most common cause of which is usually a malfunction or insufficient activity of one of the hydrolytic enzymes. This review article illustrates the current therapeutic options of LSD. These include enzyme replacement therapy, substrate reducing therapy, chaperone therapy and hematopoietic stem cell transplantation. Other promising strategies developed in recent years include gene therapy (GT) or hematopoietic stem cell GT (HSC-GT). For all of the mentioned therapies, the golden rule is that early diagnosis of the disease and initiation of treatment is essential for a good effect.
OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.
- MeSH
- COVID-19 * epidemiologie mortalita komplikace MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- registrace * MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 * MeSH
- syndrom systémové zánětlivé reakce * epidemiologie diagnóza terapie MeSH
- věk při počátku nemoci * MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
We thank Dr. Curtis for his interest and feedback [...].
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
