scholarly journals Hip Morphology in Mucolipidosis Type II

2020 ◽  
Vol 9 (3) ◽  
pp. 728 ◽  
Author(s):  
Luise Sophie Ammer ◽  
Esmeralda Oussoren ◽  
Nicole Maria Muschol ◽  
Sandra Pohl ◽  
Maria Estela Rubio-Gozalbo ◽  
...  
Keyword(s):  
Retrospective Chart Review ◽  
Systematic Evaluation ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Pelvic Radiograph ◽  
Hip Morphology ◽  
Age Dependent ◽  
Magnetic Resonance Imaging Mri ◽  
And Migration ◽  
Mucolipidosis Type

Mucolipidosis type II (MLII) is a rare lysosomal storage disorder caused by defective trafficking of lysosomal enzymes. Severe skeletal manifestations are a hallmark of the disease including hip dysplasia. This study aims to describe hip morphology and the natural course of hip pathologies in MLII by systematic evaluation of plain radiographs, ultrasounds and magnetic resonance imaging (MRI). An international two-centered study was performed by retrospective chart review. All MLII patients with at least one pelvic radiograph were included. A total of 16 patients were followed over a mean of 3.5 years (range 0.2–10.7 years). Typical age-dependent radiographic signs identified were femoral cloaking (7/16), rickets/hyperparathyroidism-like changes (6/16) and constrictions of the supra-acetabular part of the os ilium (16/16) and the femoral neck (7/16). The course of acetabular and migration indexes (AI, MI) significantly increased in female patients. However, in the overall group, there was no relevant progression of acetabular dysplasia with a mean AI of 23.0 (range 5°–41°) and 23.7° (range 5°–40°) at the first and last assessments, respectively. Better knowledge on hip morphology in MLII could lead to earlier diagnosis, improved clinical management and enables assessment of effects of upcoming therapies on the skeletal system.

scholarly journals Challenges in Diagnosing Rare Genetic Causes of Common In Utero Presentations: Report of Two Patients with Mucolipidosis Type II (I-Cell Disease)

2018 ◽  
Vol 07 (03) ◽  
pp. 134-137 ◽  
Author(s):  
Gregory Costain ◽  
Maha Saleh ◽  
Shimrit Yaniv-Salem ◽  
Greg Ryan ◽  
Eric Morgen ◽  
...  
Keyword(s):  
Single Gene ◽  
Genetic Diagnosis ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Cell Disease ◽  
Single Gene Disorders ◽  
Whole Exome ◽  
History Of ◽  
Traditional Approaches ◽  
Mucolipidosis Type

AbstractTraditional approaches to prenatal genetic diagnosis for common presentations such as short femurs or intrauterine growth restriction are imperfect, and whole-exome sequencing is an emerging option. Mucolipidosis type II (I-cell disease) is an ultra-rare autosomal recessive lysosomal storage disorder with the potential for prenatal-onset skeletal and placental manifestations. We describe the prenatal signs in two recent unrelated patients with confirmed diagnoses soon after birth. In both cases, parents were consanguineous but there was no known family history of mucolipidosis type II. False reassurance was provided after negative testing for another disease with overlapping prenatal manifestations already present in one of the families, emphasizing that offspring of consanguineous parents can be at risk for more than one recessive condition. Our experience illustrates the potential advantages in expanding prenatal applications of WES for the identification of rare single gene disorders in offspring of consanguineous unions.

scholarly journals Transgenic inhibition of interleukin-6 trans-signaling does not prevent skeletal pathologies in mucolipidosis type II mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Marie Westermann ◽  
Anke Baranowsky ◽  
Giorgia Di Lorenzo ◽  
Tatyana Danyukova ◽  
Jamie Soul ◽  
...  
Keyword(s):  
Bone Mass ◽  
Interleukin 6 ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Elevated Expression ◽  
Pharmacological Blockade ◽  
Natural Inhibitor ◽  
Membrane Bound ◽  
Soluble Fusion Protein ◽  
Mucolipidosis Type

AbstractSevere skeletal alterations are common symptoms in patients with mucolipidosis type II (MLII), a rare lysosomal storage disorder of childhood. We have previously reported that progressive bone loss in a mouse model for MLII is caused by an increased number of bone-resorbing osteoclasts, which is accompanied by elevated expression of the cytokine interleukin-6 (IL-6) in the bone microenvironment. In the present study we addressed the question, if pharmacological blockade of IL-6 can prevent the low bone mass phenotype of MLII mice. Since the cellular IL-6 response can be mediated by either the membrane-bound (classic signaling) or the soluble IL-6 receptor (trans-signaling), we first performed cell culture assays and found that both pathways can increase osteoclastogenesis. We then crossed MLII mice with transgenic mice expressing the recombinant soluble fusion protein sgp130Fc, which represents a natural inhibitor of IL-6 trans-signaling. By undecalcified histology and bone-specific histomorphometry we found that high circulating sgp130Fc levels do not affect skeletal growth or remodeling in wild-type mice. Most importantly, blockade of IL-6 trans-signaling did neither reduce osteoclastogenesis, nor increase bone mass in MLII mice. Therefore, our data clearly demonstrate that the bone phenotype of MLII mice cannot be corrected by blocking the IL-6 trans-signaling.

Ultrastructural Analysis of Neuronal and Non-neuronal Lysosomal Storage in Mucolipidosis Type II Knock-in Mice

2013 ◽  
Vol 37 (5) ◽  
pp. 366-372 ◽  
Author(s):  
Michaela Schweizer ◽  
Sandra Markmann ◽  
Thomas Braulke ◽  
Katrin Kollmann
Keyword(s):  
Ultrastructural Analysis ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucolipidosis Type

The lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: Update onGNPTABandGNPTGmutations

2019 ◽  
Author(s):  
Renata Voltolini Velho ◽  
Frederike L. Harms ◽  
Tatyana Danyukova ◽  
Nataniel F. Ludwig ◽  
Michael J. Friez ◽  
...  
Keyword(s):  
Lysosomal Storage Disorders ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Type Iii ◽  
Alpha Beta ◽  
Mucolipidosis Type ◽  
Storage Disorders

scholarly journals Placental pathology in an unsuspected case of mucolipidosis type II with secondary hyperparathyroidism in a premature infant

2021 ◽  
Vol 27 ◽  
pp. 100747
Author(s):  
Parith Wongkittichote ◽  
Garland Michael Upchurch ◽  
Louis P. Dehner ◽  
Timothy Wood ◽  
Jorge L. Granadillo
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Premature Infant ◽  
Type Ii ◽  
Placental Pathology ◽  
Mucolipidosis Type

scholarly journals Biopsychosocial issues of a patient with mucolipidosis type II

2014 ◽  
Vol 26 (1) ◽  
pp. 52-53
Author(s):  
Chin-Chen Wen ◽  
Chun-Ying Weng ◽  
Meei-Ju Lin ◽  
Shao-Yin Chu
Keyword(s):  
Type Ii ◽  
Mucolipidosis Type

Lateral Talar Process Fracture and Peroneal Tendon Dislocation: A Previously Unrecognized Injury Complex

2008 ◽  
Vol 29 (10) ◽  
pp. 1020-1024 ◽  
Author(s):  
Sandra E. Klein ◽  
Kevin E. Varner ◽  
John V. Marymont
Keyword(s):  
Retrospective Chart Review ◽  
High Energy ◽  
Activity Level ◽  
Peroneal Tendon ◽  
Type Ii ◽  
Retrospective Case ◽  
Level Of Evidence ◽  
Lateral Process ◽  
Subtalar Arthritis ◽  
Final Followup

Background: Lateral talar process fractures and peroneal tendon dislocations are frequently unrecognized at the time of injury. Lateral process fractures were initially classified by Hawkins as three types. Type II injuries are comminuted fractures involving both the talofibular and talocalcaneal articular surfaces. The purpose of this retrospective chart review was to describe an injury complex of Type II lateral talar process fracture with peroneal tendon dislocation. Materials and Methods: Between January of 1995 and December 2006, 13 patients were seen for a lateral talar process fracture. Patients' charts were reviewed for fracture classification, mechanism of injury, radiographic studies, treatment, secondary procedures, length of followup and return to previous activity level. Concurrent peroneal tendon dislocations were identified in a subset of these patients. Results: Thirteen patients were identified with lateral talar process fractures all of which were classified as a Hawkins Type II. Six patients (46%) had a simultaneous peroneal tendon dislocation. All patients underwent operative excision of the comminuted lateral process. Patients with the injury complex were more likely to undergo additional operative procedures, and were more likely to develop subtalar arthritis. At final followup, 71% of patients with isolated lateral process fractures and 33% of injury complex patients had returned to their previous level of activity Conclusion: An injury complex of Hawkins Type II lateral talar process fractures and peroneal tendon dislocation exists. Patients with comminuted lateral talar process fractures, especially those resulting from high-energy injuries, should be carefully evaluated for the possibility of concurrent peroneal tendon dislocation. Level of Evidence: IV, Retrospective Case Study

Mucolipidosis Type IV: Clinical Spectrum and Natural History

PEDIATRICS ◽  
1987 ◽  
Vol 79 (6) ◽  
pp. 953-959
Author(s):  
Naomi Amir ◽  
Joel Zlotogora ◽  
Gideon Bach
Keyword(s):  
Age Of Onset ◽  
Clinical Manifestations ◽  
Psychomotor Retardation ◽  
Clinical Spectrum ◽  
Lysosomal Storage ◽  
Mucolipidosis Type Iv ◽  
Type Iv ◽  
First Year Of Life ◽  
Developmental Features ◽  
Mucolipidosis Type

The clinical spectrum and developmental features of mucolipidosis type IV, a recessive lysosomal storage disorder, are presented. The evaluation was based on information from the clinical charts and information obtained from the families of 20 patients between the ages of 2 to 17 years. The clinical manifestations of the disease, profound psychomotor retardation and visual impairment, appear during the first year of life. Definitive diagnosis is made by electron microscopy which reveals storage organelles typical of the mucolipidoses. This study details, for the first time, the heterogeneity of the ophthalmologic features, specifically as pertains to the age of onset, degree and clinical course of the corneal opacities, and the retinal involvement. Although the top developmental level was found to be 12 to 15 months in language and motor function, the course of the disease is protracted for some children, who show only a slight improvement, and others, little if any deterioration despite the early infantile onset of the disease. This presentation provides guidelines for the clinical diagnosis of mucolipidosis type IV.

Abstract 530: Decreased NSF S-Nitrosylation in the Aorta and an Age-Dependent Endothelial Activation in Mice with Fabry Disease

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Justin J Kang ◽  
Liming Shu ◽  
Karl C Desch ◽  
Peter F Bodary ◽  
James A Shayman
Keyword(s):  
Nitric Oxide ◽  
Fabry Disease ◽  
Endothelial Activation ◽  
Lysosomal Storage ◽  
Agarose Beads ◽  
Endothelial Inflammation ◽  
Enos Uncoupling ◽  
Age Dependent ◽  
The Many ◽  
Main Component

Fabry disease is an X-linked lysosomal storage disorder caused by loss of activity of the enzyme, α-galactosidase A (GLA). The loss of GLA function leads to an age-dependent accumulation of globotriaosylceramide (Gb3) in endothelial cells. Endothelial Gb3 accumulation is associated with endothelial nitric oxide synthase (eNOS) uncoupling and decreased nitric oxide (NO) bioavailability. We hypothesized that GLA deficiency promotes endothelial inflammation. von Willebrand factor (VWF) is the main component of Weibel Palade bodies (WPB) and is secreted upon endothelial inflammation. We observed significantly elevated plasma VWF in GLA null mice (FA) compared to age-matched Wild-Type mice (WT) (p=0.046 at 2 months and p<0.001 at 5 and 17 months), indicating increased endothelial inflammation in FA. Out of the many proteins that regulate WPB exocytosis, N-ethylmaleimide sensitive factor (NSF) is a critical mediator of the exocytic machinery and a major target of NO. NO can reversibly modify NSF cysteine residues via a process called S-nitrosylation (SNO), leading to decreased WPB exocytosis. To evaluate whether GLA deficiency promotes a decrease in SNO-NSF, nitrosylated cysteines of aortic homogenates from male WT and FA were first labeled with biotin through a biotin switch assay. Next, biotinylated proteins were isolated with streptavidin-agarose beads. We observed an approximately 60% decrease in the level of SNO-NSF in the aorta of FA compared to that of WT by Western blot (WT vs. Fabry: 1.0±0.03 vs. 0.4±0.11, p=0.002, n=4-5/group) whereas total protein expression of NSF and GAPDH were not different between groups. The level of thioredoxin-1 (TRX-1) was significantly elevated in FA compared to WT (WT vs. Fabry: 1.0±0.05 vs. 1.4±0.14, p=0.01, n=6-9/group), suggesting high levels of reactive oxygen species and protein denitrosylase activity in Fabry disease. In conclusion, these results provide evidence of endothelial activation in Fabry disease. GLA deficiency resulted in decreased SNO-NSF and increased TRX-1 in parallel with the robust elevation of VWF. Future study is required for further understanding of the mechanistic links between these observations, and to determine whether this is a reversible phenomenon in the setting of Fabry disease.

scholarly journals Age-dependent formation of TMEM106B amyloid filaments in human brain

2021 ◽  
Author(s):  
Manuel Schweighauser ◽  
Diana Arseni ◽  
Melissa Huang ◽  
Sofia Lövestam ◽  
Yang Shi ◽  
...  
Keyword(s):  
Human Brain ◽  
Transmembrane Protein ◽  
Amyloid Β ◽  
Dependent Manner ◽  
Type Ii ◽  
Western Blots ◽  
Normal Individuals ◽  
Age Dependent ◽  
Neurologically Normal ◽  
Filamentous Inclusions

Many age-dependent neurodegenerative diseases, like Alzheimer's and Parkinson's, are characterised by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β (Aβ), α-synuclein and TDP-43 are the most common. Here, we used electron cryo-microscopy (cryo-EM) structure determination to show that residues 120-254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in the human brain. We solved cryo-EM structures of TMEM106B filaments from the brains of 22 individuals with neurodegenerative conditions, including sporadic and inherited tauopathies, Aβ-amyloidoses, synucleinopathies and TDP-43opathies, as well as from the brains of two neurologically normal individuals. We observed three different TMEM106B folds, with no clear relationship between folds and diseases. The presence of TMEM106B filaments correlated with that of a 29 kDa sarkosyl-insoluble fragment of the protein on Western blots. The presence of TMEM106B filaments in the brains of older, but not younger, neurologically normal individuals indicates that they form in an age-dependent manner.

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