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1.
Orphanet J Rare Dis ; 16(1): 401, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583711

RESUMO

BACKGROUND: Although the clinical efficacy of laminoplasty in adult cervical spondylotic myelopathy or ossification of posterior longitudinal ligament has been frequently reported, there are only few reports of laminoplasty for patients with lysosome storage diseases (LSDs). Therefore, this study aimed to report the midterm clinical and radiological outcomes of patients with LSDs after cervical laminoplasty. METHODS: Six patients with LSD who underwent laminoplasty with/without C1 laminectomy for cervical myelopathy were enrolled. Clinical evaluations, including the cervical Japanese Orthopedic Association (cJOA) score and visual analog scale (VAS) scores for upper extremity numbness, and radiographic parameters, including C2-C7 lordotic angle, atlanto-dens interval (ADI), and ⊿ADI, were evaluated preoperatively, at 2 years postoperatively, and at the final follow-up. RESULTS: Five patients had mucopolysaccharidoses (type I: n = 1, II: n = 3, VII: n = 1) and one patient had mucolipidoses type III. The mean age of patients at surgery was 27.5 years, and the mean postoperative follow-up period was 61 months. All mucopolysaccharidoses cases required C1 posterior arch resection with C2-C7 laminoplasty. No critical complications were observed postoperatively. There were no significant differences in C2-C7 angle (p = 0.724) and ⊿ADI (p = 0.592) between the preoperative and final follow-ups. The cJOA score and VAS for numbness significantly improved at the final follow-up (p = 0.004 and p = 0.007, respectively). CONCLUSIONS: The cervical myelopathy in patients with LSD could be safely and effectively treated with laminoplasty with/without C1 posterior arch resection after excluding patients with atlantoaxial instability. Atlantoaxial stability and symptom improvement could be maintained at an average of 5 years postoperatively.


Assuntos
Laminoplastia , Doenças por Armazenamento dos Lisossomos , Mucolipidoses , Mucopolissacaridoses , Doenças da Medula Espinal , Adulto , Vértebras Cervicais/cirurgia , Humanos , Estudos Retrospectivos , Doenças da Medula Espinal/cirurgia , Resultado do Tratamento
2.
Hum Genet ; 140(8): 1143-1156, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33974130

RESUMO

Biallelic STX3 variants were previously reported in five individuals with the severe congenital enteropathy, microvillus inclusion disease (MVID). Here, we provide a significant extension of the phenotypic spectrum caused by STX3 variants. We report ten individuals of diverse geographic origin with biallelic STX3 loss-of-function variants, identified through exome sequencing, single-nucleotide polymorphism array-based homozygosity mapping, and international collaboration. The evaluated individuals all presented with MVID. Eight individuals also displayed early-onset severe retinal dystrophy, i.e., syndromic-intestinal and retinal-disease. These individuals harbored STX3 variants that affected both the retinal and intestinal STX3 transcripts, whereas STX3 variants affected only the intestinal transcript in individuals with solitary MVID. That STX3 is essential for retinal photoreceptor survival was confirmed by the creation of a rod photoreceptor-specific STX3 knockout mouse model which revealed a time-dependent reduction in the number of rod photoreceptors, thinning of the outer nuclear layer, and the eventual loss of both rod and cone photoreceptors. Together, our results provide a link between STX3 loss-of-function variants and a human retinal dystrophy. Depending on the genomic site of a human loss-of-function STX3 variant, it can cause MVID, the novel intestinal-retinal syndrome reported here or, hypothetically, an isolated retinal dystrophy.


Assuntos
Oftalmopatias Hereditárias/genética , Mucosa Intestinal/metabolismo , Síndromes de Malabsorção/genética , Microvilosidades/patologia , Mucolipidoses/genética , Polimorfismo de Nucleotídeo Único , Proteínas Qa-SNARE/genética , Células Fotorreceptoras Retinianas Cones/metabolismo , Distrofias Retinianas/genética , Idoso , Idoso de 80 Anos ou mais , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Animais , Autopsia , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Oftalmopatias Hereditárias/metabolismo , Oftalmopatias Hereditárias/patologia , Feminino , Regulação da Expressão Gênica , Homozigoto , Humanos , Mucosa Intestinal/patologia , Síndromes de Malabsorção/metabolismo , Síndromes de Malabsorção/patologia , Camundongos , Camundongos Knockout , Microvilosidades/genética , Microvilosidades/metabolismo , Mucolipidoses/metabolismo , Mucolipidoses/patologia , Fenótipo , Proteínas Qa-SNARE/deficiência , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Fotorreceptoras Retinianas Cones/patologia , Distrofias Retinianas/metabolismo , Distrofias Retinianas/patologia , Rodopsinas Sensoriais/genética , Rodopsinas Sensoriais/metabolismo , Sequenciamento Completo do Exoma
3.
J Pediatr Gastroenterol Nutr ; 72(6): 826-832, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33976085

RESUMO

OBJECTIVES: Congenital diarrhea and enteropathies linked to epithelial structural abnormalities constitute 3 different rare diseases: the tufting enteropathies (TE; EPCAM and SPINT2 mutations), microvillous inclusion disease (MVID; MYO5B and STX3 mutations), and tricho-hepato-enteric syndrome (THE; TTC37 and SKIV2L mutations). Moreover, enteroendocrine deficiencies (ED; PCSK1 and NEUROG3 mutations) share common clinical characteristics with TE, THE, and MVID in that the treatment requires, in most cases, long-term parenteral nutrition. Although numerous cases have been reported in the literature, aggregated data on morbidity and mortality are missing owing to the rarity of the diseases. METHODS: We performed a systematic review of all published cases and retrieved 86 articles describing 323 patients (164 boys and 135 girls). RESULTS: The mortality rate was 20.28%, with a median age at death of 13.5 months (range 0-228 months); the mortality risk was 30.8/1000 person-year; in half of the cases, death was caused by infections. Parenteral nutrition was required in 95.4% of patients and weaning off from parenteral nutrition was achieved in 29.35% at a median age of 23 months (range 3.3-276 months). The patients with ED linked to PCSK1 were nearly all weaned at a median age of 14 months, but most of the patients became overweight. MVID patients with MYO5B mutations were most often born preterm. ED linked to NEUROG3 mutation and THE patients usually presented with intrauterine growth retardation. CONCLUSIONS: This review presents data from 323 patients with congenital diarrhea linked to EPCAM TE, SPINT2 TE, TTC37 THE, SKIV2L THE, MYO5B MVID, STX3 MVID, NEUROG3 ED, and PCSK1 ED mutations.


Assuntos
Diarreia Infantil , Enteropatias , Síndromes de Malabsorção , Mucolipidoses , Feminino , Humanos , Lactente , Recém-Nascido , Síndromes de Malabsorção/genética , Masculino , Glicoproteínas de Membrana , Microvilosidades
4.
Int J Mol Sci ; 22(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922276

RESUMO

Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1G227R and NEU1V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1G227R- and NEU1V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1G227R- and NEU1V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy-lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.


Assuntos
Astrócitos/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Mucolipidoses/patologia , Células-Tronco Neurais/patologia , Neuraminidase/metabolismo , Oligodendroglia/patologia , Teratoma/patologia , Astrócitos/metabolismo , Autofagia , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lisossomos , Mucolipidoses/genética , Mucolipidoses/metabolismo , Mutação , Células-Tronco Neurais/metabolismo , Neuraminidase/genética , Oligodendroglia/metabolismo , Fenótipo , Teratoma/genética , Teratoma/metabolismo
7.
Orphanet J Rare Dis ; 16(1): 39, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478506

RESUMO

BACKGROUND: Mucolipidosis type IV (MLIV), an ultra-rare neurodevelopmental and neurodegenerative disorder, is caused by mutations in the MCOLN1 gene, which encodes the late endosomal/lysosomal transient receptor potential channel TRPML1 (mucolipin 1). The precise pathophysiogical pathways that cause neurological disease in MLIV are poorly understood. Recently, the first post-mortem brain sample became available from a single MLIV patient, and in the current study we performed mass spectrometry (MS)-based proteomics on this tissue with a view to delineating pathological pathways, and to compare with previously-published data on MLIV, including studies using the Mcoln1-/- mouse. RESULTS: A number of pathways were altered in two brain regions from the MLIV patient, including those related to the lysosome, lipid metabolism, myelination, cellular trafficking and autophagy, mTOR and calmodulin, the complement system and interferon signaling. Of these, levels of some proteins not known previously to be associated with MLIV were altered, including APOD, PLIN4, ATG and proteins related to interferon signaling. Moreover, when proteins detected by proteomics in the human brain were compared with their orthologs detected in the Mcoln1-/- mouse by RNAseq, the results were remarkably similar. Finally, analysis of proteins in human and mouse CSF suggest that calbindin 1 and calbindin 2 might be useful as biomarkers to help chart the course of disease development. CONCLUSIONS: Despite the sample size limitations, our findings are consistent with the relatively general changes in lysosomal function previously reported in MLIV, and shed light on new pathways of disease pathophysiology, which is required in order to understand the course of disease development and to determine the efficacy of therapies when they become available for this devastating disease.


Assuntos
Mucolipidoses , Canais de Potencial de Receptor Transitório , Animais , Encéfalo/metabolismo , Humanos , Lisossomos/metabolismo , Camundongos , Mucolipidoses/genética , Proteômica , Canais de Potencial de Receptor Transitório/genética , Canais de Potencial de Receptor Transitório/metabolismo
8.
Cardiol Young ; 31(5): 862-864, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33507140

RESUMO

Sialidosis, a rare autosomal recessive disorder, is caused by a deficiency of NEU1 encoded enzyme alpha-N-acetyl neuraminidase. We report a premature male with neonatal-onset type II sialidosis which was associated with left ventricular dysfunction. The clinical presentation and subsequent progression which culminated in his untimely death at 16 months of age are succinctly described. Early-onset cardiovascular involvement as noted in this patient is not well characterised. The case report is supplemented by a comprehensive review of the determinants, characteristics, and the clinical course of cardiovascular involvement in this rare condition.


Assuntos
Mucolipidoses , Humanos , Recém-Nascido , Masculino , Mucolipidoses/complicações , Mucolipidoses/diagnóstico , Mucolipidoses/genética , Neuraminidase/genética , Síndrome
9.
Mol Biol Rep ; 48(2): 1465-1474, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33507475

RESUMO

Mucolipidosis III gamma (ML III γ) is a slowly progressive disorder that affects multiple parts of the body such as the skeleton, joints, and connective tissue structures. It is caused by pathogenic variants in the GNPTG gene that provides instructions for producing the γ subunit of GlcNAc-1-phosphotransferase. In this study we aim to characterize clinical findings and biological insights on two novel GNPTG variants causing ML III γ phenotypes with varying severity. We report on two siblings with ML III γ bearing the previously undescribed c.477C > G (p.Y159*) nonsense variant in a homozygous state as well as a patient with ML III γ bearing the novel c.110 + 19_111-17del variant in a homozygous state. These variants were revealed by whole-exome sequencing and Sanger sequencing, respectively. Their parents, who are heterozygotes for the same mutation, are healthy. The clinical and radiographic presentation of ML III γ in our patients who had c.477C > G (p.Y159*) variant is consistent with a relatively severe form of the disease, which is further supported by a working three-dimensional model of the GlcNAc-1-phosphotransferase γ subunit. On the other hand, it is seen that our patient who carries the c.110 + 19_111-17del variant has a milder phenotype. Our findings help broaden the spectrum of GNPTG variants causing ML III γ and offer structural and mechanistic insights into loss of GlcNAc-1-phosphotransferase γ subunit function.


Assuntos
Predisposição Genética para Doença , Mucolipidoses/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Códon sem Sentido/genética , Feminino , Homozigoto , Humanos , Articulações/patologia , Masculino , Mucolipidoses/patologia , Fenótipo , Índice de Gravidade de Doença , Irmãos , Esqueleto/patologia , Sequenciamento Completo do Exoma
11.
Bone ; 143: 115729, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33130340

RESUMO

The hips are frequently involved in inheritable diseases which affect the bones. The clinical and radiological presentation of these diseases may be very similar to common hip disorders as developmental dysplasia of the hip, osteoarthritis and avascular necrosis, so the diagnosis may be easily overlooked and treatment may be suboptimal. Mucopolysaccharidosis (MPS) and Mucolipidosis (ML II and III) are lysosomal storage disorders with multisystemic involvement. Characteristic skeletal abnormalities, known as dysostosis multiplex, are common in MPS and ML and originate from intra-lysosomal storage of glycosaminoglycans in cells of the cartilage, bones and ligaments. The hip joint is severely affected in MPS and ML. Hip pathology results in limitations in mobility and pain from young age, and negatively affects quality of life. In order to better understand the underlying process that causes hip disease in MPS and ML, this review first describes the normal physiological (embryonic) hip joint development, including the interplay between the acetabulum and the femoral head. In the second part the factors contributing to altered hip morphology and function in MPS and ML are discussed, such as abnormal development of the pelvic- and femoral bones (which results in altered biomechanical forces) and inflammation. In the last part of this review therapeutic options and future perspectives are addressed.


Assuntos
Mucolipidoses , Mucopolissacaridoses , Acetábulo , Articulação do Quadril , Humanos , Mucolipidoses/complicações , Mucopolissacaridoses/complicações , Qualidade de Vida
12.
J Pediatr ; 229: 302-304, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33038345
13.
Tokai J Exp Clin Med ; 45(4): 243-248, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33300597

RESUMO

OBJECTIVE: We generated induced pluripotent stem (iPS) cells from a patient with distal myopathy with rimmed vacuoles (DMRV), in which sialic acids synthesis is reported to be defective. In this study, we examined whether the differentiation to retinal pigment epithelial (RPE) cells and autophagy was affected in the patient derived cells. METHODS: Patient derived iPS cells were established through the transduction of re-programming factors into peripheral mononuclear cells via retrovirus vectors. RPE cells were induced from iPS cells through aggregation culture. Then the autophagy induced by amino acid starvation was estimated by measuring LC3-containing "puncta" structure. RESULTS: A 3D aggregate culture of patient-derived iPS cells resulted in some irregular shapes, and the aggregate contained large vacuoles filled with lipid droplets and cellular components such as damaged mitochondria. RPE cells induced from patient-derived iPS cells showed impaired autophagy flux under amino acid starvation. CONCLUSION: These findings were similar to those of sialidosis patient-derived iPS cells, in which cleavage of terminal sialic acids in oligosaccharide chains is defective. This suggests that the control of both the addition and removal of sialic acids are pivotal for autophagy progression.


Assuntos
Autofagia , Miopatias Distais/patologia , Células Epiteliais/fisiologia , Células-Tronco Pluripotentes/patologia , Pigmentos da Retina , Ácidos Siálicos , Vacúolos/patologia , Adulto , Aminoácidos/deficiência , Diferenciação Celular , Células Cultivadas , Miopatias Distais/etiologia , Miopatias Distais/metabolismo , Feminino , Humanos , Mucolipidoses/patologia , Oligossacarídeos/metabolismo , Células-Tronco Pluripotentes/citologia , Ácidos Siálicos/deficiência , Ácidos Siálicos/metabolismo
14.
J Biol Regul Homeost Agents ; 34(4 Suppl. 2): 71-77, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33000604

RESUMO

Mucolipidosis II and III are lysosomal storage diseases caused by pathogenetic mutations in GNPTAB and GNPTG genes which cause an impaired activity of the lysosomal hydrolase N-acetylglucosamine- 1-phosphotransferase, a key enzyme in the synthesis of the mannose-6-phosphate targeting signals on lysosomal enzymes. Patients with MLII alpha/beta present coarse facial features, cessation of statural growth, important skeletal manifestations, impaired neuromotor development and cardiorespiratory involvement. All children appear to have cardiac involvement, but severe dilated cardiomyopathy is uncommon. In this report we describe the case of an 11-month-old girl who is affected by a MLII. Analysis of the GNPTAB gene identified at a heterozygous level the previously described gene variants c. 2693delA p(Lys898Serfs*13) and c. 2956C>T p(Arg986Cys). Her main clinical features were coarse face with gingival hypertrophy, dysostosis multiplex, recurrent respiratory infection and an early onset of dilated cardiomyopathy, an uncommon feature for MLII. To our knowledge, dilated cardiomyopathy has been previously described in literature in only two cases of MLII and in one patient affected by MLIII.


Assuntos
Cardiomiopatia Dilatada , Diabetes Mellitus Tipo 2 , Mucolipidoses , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/genética , Criança , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Lactente , Mucolipidoses/complicações , Mucolipidoses/diagnóstico , Mucolipidoses/genética , Mutação , Transferases (Outros Grupos de Fosfato Substituídos)/genética
16.
JCI Insight ; 5(20)2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33055423

RESUMO

Although congenital heart defects (CHDs) represent the most common birth defect, a comprehensive understanding of disease etiology remains unknown. This is further complicated since CHDs can occur in isolation or as a feature of another disorder. Analyzing disorders with associated CHDs provides a powerful platform to identify primary pathogenic mechanisms driving disease. Aberrant localization and expression of cathepsin proteases can perpetuate later-stage heart diseases, but their contribution toward CHDs is unclear. To investigate the contribution of cathepsins during cardiovascular development and congenital disease, we analyzed the pathogenesis of cardiac defects in zebrafish models of the lysosomal storage disorder mucolipidosis II (MLII). MLII is caused by mutations in the GlcNAc-1-phosphotransferase enzyme (Gnptab) that disrupt carbohydrate-dependent sorting of lysosomal enzymes. Without Gnptab, lysosomal hydrolases, including cathepsin proteases, are inappropriately secreted. Analyses of heart development in gnptab-deficient zebrafish show cathepsin K secretion increases its activity, disrupts TGF-ß-related signaling, and alters myocardial and valvular formation. Importantly, cathepsin K inhibition restored normal heart and valve development in MLII embryos. Collectively, these data identify mislocalized cathepsin K as an initiator of cardiac disease in this lysosomal disorder and establish cathepsin inhibition as a viable therapeutic strategy.


Assuntos
Catepsina K/genética , Cardiopatias Congênitas/genética , Coração/crescimento & desenvolvimento , Mucolipidoses/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Animais , Modelos Animais de Doenças , Ativação Enzimática/genética , Predisposição Genética para Doença , Coração/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , Valvas Cardíacas/crescimento & desenvolvimento , Humanos , Doenças por Armazenamento dos Lisossomos/genética , Doenças por Armazenamento dos Lisossomos/fisiopatologia , Mucolipidoses/fisiopatologia , Mutação , Fator de Crescimento Transformador beta/genética , Peixe-Zebra/genética
17.
Int J Mol Sci ; 21(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957425

RESUMO

Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate N-acetylglucosamine: lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. The process is performed by a sequential two-step process: first, GlcNAc-1-phosphotransferase catalyzes the transfer of GlcNAc-1-phosphate to the selected mannose residues on lysosomal enzymes in the cis-Golgi network. The second step removes GlcNAc from lysosomal enzymes by N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (uncovering enzyme) and exposes the mannose 6-phosphate (M6P) residues in the trans-Golgi network, in which the enzymes are targeted to the lysosomes by M6Preceptors. A deficiency of GlcNAc-1-phosphotransferase causes the hypersecretion of lysosomal enzymes out of cells, resulting in a shortage of multiple lysosomal enzymes within lysosomes. Due to a lack of GlcNAc-1-phosphotransferase, the accumulation of cholesterol, phospholipids, glycosaminoglycans (GAGs), and other undegraded substrates occurs in the lysosomes. Clinically, ML II and ML III exhibit quite similar manifestations to mucopolysaccharidoses (MPSs), including specific skeletal deformities known as dysostosis multiplex and gingival hyperplasia. The life expectancy is less than 10 years in the severe type, and there is no definitive treatment for this disease. In this review, we have described the updated diagnosis and therapy on ML II/III.


Assuntos
Terapia de Reposição de Enzimas/métodos , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Lisossomos/metabolismo , Mucolipidoses/diagnóstico , Animais , Transporte Biológico Ativo , Modelos Animais de Doenças , Glicosaminoglicanos/metabolismo , Humanos , Manosefosfatos/metabolismo , Mucolipidoses/enzimologia , Mucolipidoses/fisiopatologia , Mucolipidoses/terapia
18.
BMC Ophthalmol ; 20(1): 356, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867703

RESUMO

BACKGROUND: Sialidosis is a rare genetic lysosomal storage disorder caused by a deficit of neuraminidase enzyme activity. Patients with sialidosis present various neurological disorders such as: myoclonic epilepsy and hypotonia, often associated with visual impairment. A typical aspect of sialidosis is the finding of a macular cherry-red spot on ocular fundus examination. In this paper we describe a unilateral case of Bergmeister's papilla (BP) in a young female patient suffering from type 1 sialidosis. CASE PRESENTATION: A 28-year-old young woman suffering from type 1 sialidosis, confirmed by previously described compound heterozigosity Leu91Arg and Gly328Ser on N-acetyl-alpha-neuraminidase - 1 (NEU1) gene, underwent an opthalmological examination at the Eye Clinic of the University of Campania L. Vanvitelli, for bilateral visual deterioration. The patient was suffering from myoclonic epilepsy with hypotonia and severe motor disability. Fundoscopic examination showed a typical macular cherry-red spot with retinal pigment epithelium dystrophy in the middle periphery, in both eyes. Furthermore, in the left eye (OS), a vitreous thickening was observed in the nasal sector of the optic disc, remnant of fetal vasculature on the optic disc (Bergmeister's papilla). Optical coherence tomography (OCT) showed, in both eyes, a thickening of the ganglion cell layer (GCL) with a hyperreflective opacity as a cap on the left optic disc. CONCLUSIONS: In our paper we have described, for the first time in literature, a case of BP in a patient with type 1 sialidosis. The detection of BP with thickening of the peripapillary vitreous by SD-OCT is useful in monitoring any vitreo-retinal change that could cause future visual deterioration.


Assuntos
Pessoas com Deficiência , Transtornos Motores , Mucolipidoses , Disco Óptico , Adulto , Feminino , Humanos , Mucolipidoses/diagnóstico , Mucolipidoses/genética , Tomografia de Coerência Óptica
19.
Int J Mol Sci ; 21(17)2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32842549

RESUMO

The endosomal recycling pathway lies at the heart of the membrane trafficking machinery in the cell. It plays a central role in determining the composition of the plasma membrane and is thus critical for normal cellular homeostasis. However, defective endosomal recycling has been linked to a wide range of diseases, including cancer and some of the most common neurological disorders. It is also frequently subverted by many diverse human pathogens in order to successfully infect cells. Despite its importance, endosomal recycling remains relatively understudied in comparison to the endocytic and secretory transport pathways. A greater understanding of the molecular mechanisms that support transport through the endosomal recycling pathway will provide deeper insights into the pathophysiology of disease and will likely identify new approaches for their detection and treatment. This review will provide an overview of the normal physiological role of the endosomal recycling pathway, describe the consequences when it malfunctions, and discuss potential strategies for modulating its activity.


Assuntos
Endossomos/metabolismo , Neoplasias/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Sistemas de Liberação de Medicamentos/métodos , Endocitose/fisiologia , Endossomos/efeitos dos fármacos , Humanos , Síndromes de Malabsorção/metabolismo , Síndromes de Malabsorção/patologia , Microvilosidades/metabolismo , Microvilosidades/patologia , Mucolipidoses/metabolismo , Mucolipidoses/patologia , Neoplasias/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Transporte Proteico/fisiologia , Via Secretória , Proteínas rab de Ligação ao GTP/metabolismo
20.
Can J Cardiol ; 36(12): 1978.e1-1978.e3, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32818557

RESUMO

Mucolipidosis type III α/ß is an autosomal recessive lysosomal storage disease, caused by the deficient activity of UDP-N-acetyl glucosamine-1-phosphotransferase. The resultant intralysosomal accumulation of partly degraded mucopolysaccharides and sphingolipids causes multiple-organ damage, including the heart. The most documented cardiac manifestation is the thickening and insufficiency of mitral and aortic valves, but there are very few reports about the myocardial involvement. We report a case with mucolipidosis type III α/ß complicated by marked dilatation and dysfunction of the right ventricle, which is quite rare and further broadens the clinical spectrum of the disease.


Assuntos
Insuficiência da Valva Aórtica , Cardiomegalia , Diuréticos/administração & dosagem , Ventrículos do Coração , Insuficiência da Valva Pulmonar , Disfunção Ventricular Direita , Adulto , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/etiologia , Dilatação Patológica , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Mucolipidoses/diagnóstico , Tamanho do Órgão , Administração dos Cuidados ao Paciente/métodos , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/fisiopatologia , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/terapia
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