scholarly journals Case Report: Cerebral Revascularization in a Child With Mucopolysaccharidosis Type I

2021 ◽  
Vol 9 ◽  
Author(s):  
Nathan Grant ◽  
J. Michael Taylor ◽  
Zach Plummer ◽  
Kasiani Myers ◽  
Thomas Burrow ◽  
...  
Keyword(s):  
Cord Compression ◽  
Neurological Symptoms ◽  
Cerebral Revascularization ◽  
Type I ◽  
Lysosomal Storage ◽  
Multisystem Disease ◽  
Patient Reported ◽  
History Of ◽  
Recurrent Strokes ◽  
Mps I

Mucopolysaccharidosis (MPS) type I is a rare lysosomal storage disorder caused by an accumulation of glycosaminoglycans (GAGs) resulting in multisystem disease. Neurological morbidity includes hydrocephalus, spinal cord compression, and cognitive decline. While many neurological symptoms have been described, stroke is not a widely-recognized manifestation of MPS I. Accordingly, patients with MPS I are not routinely evaluated for stroke, and there are no guidelines for managing stroke in patients with this disease. We report the case of a child diagnosed with MPS I who presented with overt stroke and repeated neurological symptoms with imaging findings for severe ventriculomegaly, infarction, and bilateral terminal carotid artery stenosis. Direct intracranial pressure evaluation proved negative for hydrocephalus. The patient was subsequently treated with cerebral revascularization and at a 3-year follow-up, the patient reported no further neurological events or new ischemia on cerebral imaging. Cerebral arteriopathy in patients with MPS I may be associated with GAG accumulation within the cerebrovascular system and may predispose patients to recurrent strokes. However, further studies are required to elucidate the etiology of cerebrovascular arteriopathy in the setting of MPS I. Although the natural history of steno-occlusive arteriopathy in patients with MPS I remains unclear, our findings suggest that cerebral revascularization is a safe treatment option that may mitigate the risk of future strokes and should be strongly considered within the overall management guidelines for patients with MPS I.

scholarly journals Neonatal Screening for MPS Disorders in Latin America: A Survey of Pilot Initiatives

2020 ◽  
Vol 6 (4) ◽  
pp. 90
Author(s):  
Francyne Kubaski ◽  
Inês Sousa ◽  
Tatiana Amorim ◽  
Danilo Pereira ◽  
Joe Trometer ◽  
...  
Keyword(s):  
Latin America ◽  
Newborn Screening ◽  
Treatment Options ◽  
Digital Microfluidics ◽  
Premature Death ◽  
Lysosomal Storage ◽  
Pilot Studies ◽  
The Usa ◽  
History Of ◽  
Mps I

Newborn screening enables the diagnosis of treatable disorders at the early stages, and because of its countless benefits, conditions have been continuously added to screening panels, allowing early intervention, aiming for the prevention of irreversible manifestations and even premature death. Mucopolysaccharidoses (MPS) are lysosomal storage disorders than can benefit from an early diagnosis, and thus are being recommended for newborn screening. They are multisystemic progressive disorders, with treatment options already available for several MPS types. MPS I was the first MPS disorder enrolled in the newborn screening (NBS) panel in the USA and a few other countries, and other MPS types are expected to be added. Very few studies about NBS for MPS in Latin America have been published so far. In this review, we report the results of pilot studies performed in Mexico and Brazil using different methodologies: tandem mass spectrometry, molecular analysis, digital microfluidics, and fluorimetry. These experiences are important to report and discuss, as we expect to have several MPS types added to NBS panels shortly. This addition will enable timely diagnosis of MPS, avoiding the long diagnostic odyssey that is part of the current natural history of this group of diseases, and leading to a better outcome for the affected patients.

scholarly journals Differences in MPS I and MPS II Disease Manifestations

2021 ◽  
Vol 22 (15) ◽  
pp. 7888
Author(s):  
Christiane S. Hampe ◽  
Brianna D. Yund ◽  
Paul J. Orchard ◽  
Troy C. Lund ◽  
Jacob Wesley ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Treatment Options ◽  
Neurological Involvement ◽  
Type I ◽  
Ionic Balance ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Corneal Clouding ◽  
Mps I

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

Severe cardiac involvement in Gaucher type IIIC: a case report and review of the literature

2017 ◽  
Vol 27 (7) ◽  
pp. 1426-1429 ◽  
Author(s):  
Yılmaz Kör ◽  
Mehmet Keskin ◽  
Osman Başpınar
Keyword(s):  
Gaucher Disease ◽  
Autosomal Recessive ◽  
Cardiac Involvement ◽  
Late Onset ◽  
Neurological Symptoms ◽  
Type I ◽  
Lysosomal Storage ◽  
Cardiovascular Involvement ◽  
Eye Movement Disorders ◽  
Type Iiic

AbstractGaucher disease is an autosomal-recessive lysosomal storage disease characterised by the accumulation of glucocerebroside in macrophages; it is caused by mutations in glucocerebrosidase gene-1 in many organ tissues such as the liver, spleen, and bone marrow. Its different clinical subtypes, according to the presence and severity of neurological symptoms, are as follows: type I, non-neuronopathic (95%); type II, acute neuronopathic; and type III, chronic neuronopathic. Type IIIC is a rare subgroup characterised by cardiovascular involvement as well as eye-movement disorders and late-onset neurological symptoms. In such cases, homozygous D409H is the most frequently detected mutation. In this article, we report the case of a patient, aged 15 years and 8 months, with complaints of syncope and a diagnosis of type IIIC Gaucher disease.

Evidence that glycosaminoglycan storage and collagen deposition in the cauda epididymidis does not impair sperm viability in the Mucopolysaccharidosis type I mouse model

2020 ◽  
Vol 32 (3) ◽  
pp. 304 ◽  
Author(s):  
Cinthia Castro do Nascimento ◽  
Odair Aguiar ◽  
Gustavo Monteiro Viana ◽  
Vânia D'Almeida
Keyword(s):  
Sperm Morphology ◽  
Reproductive Age ◽  
Morphologic Change ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Cauda Epididymidis ◽  
Mps I

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by a deficiency of the lysosomal hydrolase, α-L-iduronidase (IDUA). IDUA degrades heparan and dermatan sulfates, two types of glycosaminoglycan (GAG), important signalling and structural molecules of the extracellular matrix. Because many cell types store GAGs, MPS I has been investigated in human and animal models. Enzyme replacement therapy is available for MPS I patients and has improved their life expectancy, allowing them to achieve reproductive age. The aim of this study was to evaluate epididymal and sperm morphology and function in a murine model of MPS I. We used C57BL Idua+/+ and Idua−/− adult male mice (6 months old) to investigate epididymal morphology, sperm ultrastructure, GAG characterisation and mating competence. Epithelial GAG storage, especially in the cauda epididymidis, was seen in Idua−/− mice. Regardless of the morphologic change and GAG storage found in the cauda epididymis, sperm morphology and motility were normal, similar to wild types. In the interstitium, vacuolated cells were found in addition to deposits of GAGs. Mating was not impaired in Idua−/− males and litter sizes were similar between groups. At the time point of the disease evaluated, the deficiency in IDUA affected the morphology of the epididymis in male Idua−/− mice, whereas sperm appearance and motility and the male’s capacity to mate and impregnate females were preserved.

scholarly journals Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

2020 ◽  
Vol 21 (4) ◽  
pp. 1459 ◽  
Author(s):  
Gustavo Monteiro Viana ◽  
Esteban Alberto Gonzalez ◽  
Marcela Maciel Palacio Alvarez ◽  
Renan Pelluzzi Cavalheiro ◽  
Cinthia Castro do Nascimento ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Dermatan Sulfate ◽  
Fluorescent Microscopy ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Lysosomal Storage ◽  
App Processing ◽  
Mps I

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of α-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of β-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration.

Neurological and chest symptoms following sclerotherapy: A single centre experience

2013 ◽  
Vol 29 (9) ◽  
pp. 619-627 ◽  
Author(s):  
Douglas A Hill
Keyword(s):  
Adverse Events ◽  
Neurological Symptoms ◽  
Direct Vision ◽  
Study Patient ◽  
Ultrasound Guided ◽  
Single Centre ◽  
Foam Sclerotherapy ◽  
Increased Risk ◽  
Patient Reported ◽  
History Of

Objectives Documentation and analysis of adverse neurological and chest symptoms in a large single centre series of sclerotherapy treatments. Method In this retrospective study, patient-reported adverse events occurring during liquid or foam sclerotherapy were recorded over a 30 month period and subsequently analyzed. The relevant patient records were reviewed to determine patient characteristics, treatment details and results of subsequent investigations. Results A total of 1744 ultrasound guided sclerotherapy treatments were performed during the study period. Almost all treatments were done with air-based sodium tetradecyl sulphate foam. During the same time period, 6504 direct vision surface vein sclerotherapy treatments were completed. Approximately 1/4 of these utilized air-based foam in varying concentrations. There were 14 adverse events in 14 patients involving neurological or chest symptoms for an incidence of 0.17%. Five patients injected with foam complained of isolated chest discomfort, tightness or shortness of breath. Nine patients reported various brief neurological symptoms. These events occurred with both liquid and foam, although the majority involved foam. More neurological events were associated with direct vision sclerotherapy of smaller superficial veins than with ultrasound guided injection of intrafascial truncular veins. Seven patients who experienced neurological symptoms had a history of migraine. Five of the patients who had neurological events were investigated for right to left shunts and found to be positive. Conclusions These events were uncommon and brief. The incidence of neurological and chest symptoms was higher with foam sclerotherapy than with liquid. A history of migraine with aura was associated with an increased risk of post-treatment neurological symptoms. Events occurred with both large vein and small vein treatment. Some events were associated with liquid sclerotherapy rather than foam and with carbon dioxide based foam as well as air foam. There were no long-term adverse consequences.

PATIENT-REPORTED OUTCOMES IN RARE LYSOSOMAL STORAGE DISEASES: KEY INFORMANT INTERVIEWS AND A SYSTEMATIC REVIEW PROTOCOL

2016 ◽  
Vol 32 (6) ◽  
pp. 393-399
Author(s):  
Patricia A. Miller ◽  
Sohail M. Mulla ◽  
Thomasin Adams-Webber ◽  
Yasmin Sivji ◽  
Gordon H. Guyatt ◽  
...  
Keyword(s):  
Systematic Review ◽  
Patient Reported Outcomes ◽  
Lysosomal Storage Diseases ◽  
Type I ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Patient Reported ◽  
Challenges And Opportunities ◽  
The Impact ◽  
Disease Specific

Objectives: To investigate the use, challenges and opportunities associated with using patient-reported outcomes (PROs) in studies with patients with rare lysosomal storage diseases (LSDs), we conducted interviews with researchers and health technology assessment (HTA) experts, and developed the methods for a systematic review of the literature. The purpose of the review is to identify the psychometrically sound generic and disease-specific PROs used in studies with patients with five LSDs of interest: Fabry, Gaucher (Type I), Niemann-Pick (Type B) and Pompe diseases, and mucopolysaccharidosis (Types I and II).Methods: Researchers and HTA experts who responded to an email invitation participated in a telephone interview. We used qualitative content analysis to analyze the anonymized transcripts. We conducted a comprehensive literature search for studies that used PROs to investigate burden of disease or to assess the impact of interventions across the five LSDs of interest.Results: Interviews with seven researchers and six HTA experts representing eight countries revealed five themes. These were: (i) the importance of using psychometrically sound PROs in studies with rare diseases, (ii) the paucity of disease-specific PROs, (iii) the importance of having PRO data for economic analyses, (iv) practical and psychometric limitations of existing PROs, and (v) suggestions for new PROs. The systematic review has been completed.Conclusions: The interviews highlight current challenges and opportunities experienced by researchers and HTA experts involved in work with rare LSDs. The ongoing systematic review will highlight the experience, opportunities, and limitations of PROs in LSDs and provide suggestions for future research.

scholarly journals Sexual behaviour in a murine model of Mucopolysaccharidosis type I (MPS I)

2019 ◽  
Author(s):  
Ana Beatriz Barbosa Mendes ◽  
Cinthia Castro do Nascimento ◽  
Vânia D’ Almeida
Keyword(s):  
Sexual Behaviour ◽  
Heparan Sulphate ◽  
Adult Life ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Lysosomal Storage ◽  
Cell Functions ◽  
Mps I ◽  
Copulatory Behaviour

AbstractMucopolysaccharidosis Type I (MPS I) is a rare genetic lysosomal storage disease caused by a mutation of IDUA gene. IDUA codes for α-L-iduronidase (IDUA), a lysosomal hydrolase that degrades glycosaminoglycans (GAGs): heparan sulphate and dermatan sulphate. GAGs are structural and signalling molecules that have a crucial role in controlling a variety of cell functions and their interaction with extracellular matrix. Because of GAG’s widespread action in cellular metabolism, MPS I is a progressive and disabling multisystemic disorder. Nowadays, the therapies availability allowed patients to reach the adult life and the consequences of the disease in their reproductive system is still little known. We aimed to investigate whether IDUA disruption influences sexual behaviour and sexual steroid production in male and female MPS I mice. We used 3 and 6-month-old male and 3-month-old female Idua+/_ and Idua−/− mice to evaluate typical rodent copulatory behaviours. In males we observed the frequency and latency of mounts, intromissions and ejaculations. In females we evaluated the lordosis quotient. We also analysed the locomotor capacity of mice in the open field test, since copulatory behaviour requires mobility. We also quantified steroidal hormonal levels in plasmatic samples. We detected an increase in the latencies of intromissions in male copulatory behaviour of Idua−/− males when compared to Idua+/_. However, the number of intromissions was not statistically different between groups. No parameter of female sexual behaviour was statistically different between control and knockout females. In both sexes, we detected diminished mobility in Idua−/− mice. Plasma hormone levels did not differ between Idua+/_ and Idua−/− mice, both in males and females. We concluded that in the considered time point of MPS I progression, mice are able to perform sexual behaviour, but the male performance may be influenced due to the motor disability predicted to MPS I.

scholarly journals Characteristics and management of pain in patients with Klippel-Feil syndrome: analysis of a global patient-reported registry

2020 ◽  
Vol 32 (4) ◽  
pp. 578-583 ◽  
Author(s):  
Kishan Patel ◽  
Hardy Evans ◽  
Samuel Sommaruga ◽  
Pia Vayssiere ◽  
Tariq Qureshi ◽  
...  
Keyword(s):  
Pain Relief ◽  
Cervical Vertebrae ◽  
Neurological Symptoms ◽  
Type I ◽  
Global Database ◽  
Type Iii ◽  
Migraine Pain ◽  
Wilcoxon Rank Sum Test ◽  
Experienced Pain ◽  
Patient Reported

OBJECTIVEKlippel-Feil syndrome (KFS) is characterized by congenital fusion of the cervical vertebrae. Due to its rarity, minimal research has been done to assess the quality and management of pain associated with this disorder. Using a large global database, the authors report a detailed analysis of the type, location, and treatment of pain in patients with KFS.METHODSData were obtained from the Coordination of Rare Diseases at Stanford registry and Klippel-Feil Syndrome Freedom registry. The cervical fusions were categorized into Samartzis type I, II, or III. The independent-sample t-test, Wilcoxon rank-sum test, and Friedman test were conducted, with significance set at p < 0.05.RESULTSSeventy-five patients (60 female, 14 male, and 1 unknown) were identified and classified as having the following types of Samartzis fusion: type I, n = 21 (28%); type II, n = 15 (20%); type III, n = 39 (52%). Seventy participants (93.3%) experienced pain associated with their KFS. The median age of patients at pain onset was 16.0 years (IQR 6.75–24.0 years), and the median age when pain worsened was 28.0 years (IQR 15.25–41.5 years). Muscle, joint, and nerve pain was primarily located in the shoulders/upper back (76%), neck (72%), and back of head (50.7%) and was characterized as tightness (73%), dull/aching (67%), and tingling/pins and needles (49%). Type III fusions were significantly associated with greater nerve pain (p = 0.02), headache/migraine pain (p = 0.02), and joint pain (p = 0.03) compared to other types of fusion. Patients with cervical fusions in the middle region (C2–6) tended to report greater muscle, joint, and nerve pain (p = 0.06). Participants rated the effectiveness of oral over-the-counter medications as 3 of 5 (IQR 1–3), oral prescribed medications as 3 of 5 (IQR 2–4), injections as 2 of 5 (IQR 1–4), and surgery as 3 of 5 (IQR 1–4), with 0 indicating the least pain relief and 5 the most pain relief. Participants who pursued surgical treatment reported significantly more comorbidities (p = 0.02) and neurological symptoms (p = 0.01) than nonsurgically treated participants and were significantly older when pain worsened (p = 0.03), but there was no difference in levels of muscle, joint, or nerve pain (p = 0.32); headache/migraine pain (p = 0.35); total number of cervical fusions (p = 0.77); location of fusions; or age at pain onset (p = 0.16).CONCLUSIONSMore than 90% of participants experienced pain. Participants with an increased number of overall cervical fusions or multilevel, contiguous fusions reported greater levels of muscle, joint, and nerve pain. Participants who pursued surgery had more comorbidities and neurological symptoms, such as balance and gait disturbances, but did not report more significant pain than nonsurgically treated participants.

Clinical Characteristics of Patients Diagnosed with Strongyloidiasis in a United States Urban Outpatient Dermatology Department: A Case Series

2017 ◽  
Vol 1 (3) ◽  
pp. 156-160
Author(s):  
Jacqueline Watchmaker ◽  
Sean Legler ◽  
Dianne De Leon ◽  
Vanessa Pascoe ◽  
Robert Stavert
Keyword(s):  
United States ◽  
Case Series ◽  
The United States ◽  
Screening Tools ◽  
Dermatology Department ◽  
Cutaneous Manifestations ◽  
Serologic Testing ◽  
Patient Reported ◽  
History Of ◽  
Endemic Areas

Background: Although considered a tropical disease, strongyloidiasis may be encountered in non-endemic regions, primarily amongst immigrants and travelers from endemic areas.  Chronic strongyloides infection may be under-detected owing to its non-specific cutaneous presentation and the low sensitivity of commonly used screening tools. Methods: 18 consecutive patients with serologic evidence of strongyloides infestation who presented to a single urban, academic dermatology clinic between September 2013 and October 2016 were retrospectively included.  Patient age, sex, country of origin, strongyloides serology titer, absolute eosinophil count, presenting cutaneous manifestations, and patient reported subjective outcome of pruritus after treatment were obtained via chart review.  Results: Of the 18 patients, all had non-specific pruritic dermatoses, 36% had documented eosinophila and none were originally from the United States. A majority reported subjective improvement in their symptoms after treatment. Conclusion:  Strongyloides infection and serologic testing should be considered in patients living in non-endemic regions presenting with pruritic dermatoses and with a history of exposure to an endemic area.Key Points:Chronic strongyloidiasis can be encountered in non-endemic areas and clinical manifestations are variableEosinophilia was not a reliable indicator of chronic infection in this case series Dermatologists should consider serologic testing for strongyloidiasis in patients with a history of exposure and unexplained pruritus

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