scholarly journals A pilot trial of deferiprone in pantothenate kinase-associated neurodegeneration patients

2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Mohammad Rohani ◽  
Saeed Razmeh ◽  
Gholam Ali Shahidi ◽  
Maryam Orooji
Keyword(s):  
Autosomal Recessive ◽  
Rating Scales ◽  
Autosomal Recessive Disease ◽  
Pilot Trial ◽  
Qualitative Evaluation ◽  
Iron Chelator ◽  
Pantothenate Kinase ◽  
Iron Load ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Pantothenate kinase-associated neurodegeneration (PKAN) is the most common form of neurodegeneration with brain iron accumulation, it is an autosomal recessive disease due to mutation in PANK 2 on chromosome 20, which causes the accumulation of iron in basal ganglia and production of free radicals that cause degeneration of the cells. Deferiprone is an iron chelator that was used in treatment of thalassemia patients, it can cross the blood-brain barrier and reverse the iron deposition in the brain. Five patients with genetically confirmed PKAN received 15 mg/kg deferiprone twice daily. All patients were examined at baseline, 12 and 18 months and magnetic resonance imaging (MRI) was done at the baseline and after 18 months. In our study qualitative evaluation of MRI showed that deferiprone was able to reduce the iron load in globus pallidus of all the patients and the results of clinical rating scales show that in four patients, there is an improvement in the first 12 months. The results of our paper show that deferiprone can prevent the progression of the disease.

Bovine β-mannosidosis: Pathologic and Genetic Findings in Salers Calves

1993 ◽  
Vol 30 (2) ◽  
pp. 130-139 ◽  
Author(s):  
L. Bryan ◽  
S. Schmutz ◽  
S. D. Hodges ◽  
F. F. Snyder
Keyword(s):  
Autosomal Recessive ◽  
Storage Disease ◽  
Autosomal Recessive Disease ◽  
Pedigree Analysis ◽  
Lymphoid Tissues ◽  
Lysosomal Storage ◽  
Gestational Weight ◽  
Head Tremor ◽  
Renal Enlargement ◽  
The Brain

β-mannosidosis is a recently recognized lysosomal storage disease in newborn Salers calves. Fourteen calves with β-mannosidase deficiency were examined. Twelve calves were from routine laboratory submissions, and two calves were the result of a breeding trial. Salers calves with β-mannosidase deficiency were of normal gestational weight, 36 ± 6 kg, but were affected at birth. The head was moderately domed, and there was mild superior brachygnathism. The calves were recumbent and had a head tremor. There was bilateral renal enlargement, severe hypomyelination in the brain and variable thyroid gland enlargement. Severe cytoplasmic vacuolation was present within neurons, tubule epithelial cells, follicular cells and macrophages of the nervous, renal, thyroid and lymphoid tissues, respectively. Pedigree analysis and breeding trial results were consistent with an autosomal recessive disease. An initial biochemical survey of 1,494 Salers cattle indicated a carrier frequency of 23%.

scholarly journals MRI and ¹H-MRS findings of three patients with Sjögren-Larsson syndrome

2006 ◽  
Vol 64 (2b) ◽  
pp. 398-401 ◽  
Author(s):  
Mauro Nakayama ◽  
Daniel G.F. Távora ◽  
Thereza C.L. Alvim ◽  
Alexandre C.B. Araújo ◽  
Rômulo L. Gama
Keyword(s):  
Autosomal Recessive ◽  
Fatty Aldehyde ◽  
Periventricular White Matter ◽  
Congenital Ichthyosis ◽  
Neurocutaneous Disorder ◽  
Magnetic Resonance Imaging Mri ◽  
Clinical Triad ◽  
Classical Triad ◽  
Larsson Syndrome ◽  
The Brain

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder caused by deficiency of the microsomal enzyme fatty aldehyde dehydrogenase. Patients present the classical triad of congenital ichthyosis, mental retardation and spastic di- or tetraplegia. Magnetic resonance imaging (MRI) of the brain usually shows hypomyelination involving the periventricular white matter. Cerebral proton MR spectroscopy (¹H-MRS) reveals a characteristic abnormal lipid peak. We report three cases of SLS from different families with the typical clinical triad. The MRI and ¹H-MRS findings are discussed.

scholarly journals Phenotypic expression and founder effect of PANK2 c.1583C>T (p.T528M) mutation in Serbian pantothenate kinase-associated neurodegeneration patients

2019 ◽  
Vol 71 (2) ◽  
pp. 275-280
Author(s):  
Marina Svetel ◽  
Monika Hartig ◽  
Dragana Cvetkovic ◽  
Cyrielle Beaubois ◽  
Jasmina Maksic ◽  
...  
Keyword(s):  
Founder Effect ◽  
Autosomal Recessive ◽  
Common Ancestor ◽  
Phenotypic Expression ◽  
Autosomal Recessive Disorder ◽  
Clinical Findings ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pantothenate Kinase ◽  
The Brain

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by dystonia, parkinsonism, cognitive and visual impairment, and iron accumulation in the brain. Many cases of PKAN result from mutations in the PANK2 gene that encodes pantothenate kinase 2, a key regulatory enzyme in the biosynthesis of coenzyme A. We previously detected six Serbian patients with clinically suggestive PKAN, all of whom had PANK2 c.1583C>T (p.T528M) mutation either in the homozygous or in the heterozygous state. In this study we explored the phenotypic expression and a possible founder effect of this substitution. We performed the analysis of linkage disequilibrium (LD) and organization in haplotypes of 23 single nucleotide polymorphisms (SNPs) adjacent to the PANK2 gene in all of the six patients and their parents, as well as in control healthy child-parents trios. The age of PANK2 c.1583C>T mutation was determined using the r2 degeneration method. Clinical findings in our patients were markedly similar. Different LD structures between patients and controls is revealed, and PANK2 c.1583T allele was significantly associated with a particular haplotype. The age of PANK2 c.1583C>T mutation was estimated to be about 15 generations. Our results suggest that PANK2 c.1583C>T in Serbian PKAN patients represents a founder mutation descended from one common ancestor.

Bilateral Striatal Necrosis with Polyneuropathy with a Novel SLC25A19 (Mitochondrial Thiamine Pyrophosphate Carrier OMIMI*606521) Mutation: Treatable Thiamine Metabolic Disorder—A Report of Two Indian Cases

2019 ◽  
Vol 50 (05) ◽  
pp. 313-317 ◽  
Author(s):  
Vykuntaraju K. Gowda ◽  
Varunvenkat M. Srinivasan ◽  
Kapil Jehta ◽  
Maya D. Bhat
Keyword(s):  
Gene Mutations ◽  
Febrile Illness ◽  
Flaccid Paralysis ◽  
Thiamine Pyrophosphate ◽  
Homozygous Mutation ◽  
Missense Variation ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Generation Sequencing ◽  
Striatal Necrosis

Abstract Background SLC25A19 gene mutations cause Amish congenital lethal microcephaly and bilateral striatal necrosis with polyneuropathy. We are reporting two cases of bilateral striatal necrosis with polyneuropathy due to SLC25A19 gene mutations. Methods A 36-month-old boy and a 5-year-old girl, unrelated, presented with recurrent episodes of flaccid paralysis and encephalopathy following nonspecific febrile illness. Examination showed dystonia and absent deep tendon reflexes. Results Nerve conduction studies showed an axonal polyneuropathy. Magnetic resonance imaging (MRI) of the brain in both cases showed signal changes in the basal ganglia. Next-generation sequencing revealed a novel homozygous missense variation c.910G>A (p.Glu304Lys) in the SLC25A19 gene in the boy and a homozygous mutation c.869T > A (p. Leu290Gln) in the SLC25A19 gene in the girl. Mutations were validated by Sanger sequencing, and carrier statuses of parents of both children were confirmed. Both children improved with thiamine supplementation. Conclusion If any child presents with recurrent encephalopathy with flaccid paralysis, dystonia, and neuropathy, a diagnosis of bilateral striatal necrosis with polyneuropathy due to SLC25A19 mutations should be considered and thiamine should be initiated.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

scholarly journals Combination of Novel c.3484G> T/p.Glu162Ter Variant in ABCB11 and c.208G> A/p.Asp70Asn Variant in ATP8B1 Are Associated with Severe Symptoms in Progressive Family Intrahepatic Cholestasis

2020 ◽  
Vol 09 (04) ◽  
pp. 285-288
Author(s):  
Mervan Bekdas ◽  
Guray Can ◽  
Recep Eroz ◽  
Selma Erdogan Duzcu
Keyword(s):  
Intrahepatic Cholestasis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Bile Secretion ◽  
Peripheral Blood Sample ◽  
Portal Fibrosis ◽  
Traditional Treatment ◽  
Pathogenic Variants ◽  
Chronic Cholestasis ◽  
Whole Exome

AbstractProgressive family intrahepatic cholestasis (PFIC) is an autosomal recessive disease that causes chronic cholestasis. It is associated with pathogenic variants in genes that encode proteins involved in bile secretion to canaliculus from hepatocytes. In this study, we present a 16-year-old boy who presented with severe pruritus and cholestatic jaundice. All possible infectious etiologies were negative. A liver biopsy was consistent with intrahepatic cholestasis and portal fibrosis. DNA was isolated from a peripheral blood sample, and whole exome sequencing was performed. A novel c.3484G > T/p.Glu162Ter variant in the ABCB11 gene and a c.208G> A/p.Asp70Asn variant in the ATP8B1 gene were detected. Despite traditional treatment, the patient's recurrent severe symptoms did not improve. The patient was referred for a liver transplantation. This novel c.3484G > T/p.Glu162Ter variant is associated with a severe and recurrent presentation, and the two compound variants could explain the severity of PFIC.

scholarly journals An improved framework for brain tumor analysis using MRI based on YOLOv2 and convolutional neural network

2021 ◽  
Author(s):  
Muhammad Irfan Sharif ◽  
Jian Ping Li ◽  
Javeria Amin ◽  
Abida Sharif
Keyword(s):  
Brain Tumor ◽  
Tumor Detection ◽  
Entropy Method ◽  
Feature Extraction And Selection ◽  
Tumor Region ◽  
Selection For ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Complicated Task

AbstractBrain tumor is a group of anomalous cells. The brain is enclosed in a more rigid skull. The abnormal cell grows and initiates a tumor. Detection of tumor is a complicated task due to irregular tumor shape. The proposed technique contains four phases, which are lesion enhancement, feature extraction and selection for classification, localization, and segmentation. The magnetic resonance imaging (MRI) images are noisy due to certain factors, such as image acquisition, and fluctuation in magnetic field coil. Therefore, a homomorphic wavelet filer is used for noise reduction. Later, extracted features from inceptionv3 pre-trained model and informative features are selected using a non-dominated sorted genetic algorithm (NSGA). The optimized features are forwarded for classification after which tumor slices are passed to YOLOv2-inceptionv3 model designed for the localization of tumor region such that features are extracted from depth-concatenation (mixed-4) layer of inceptionv3 model and supplied to YOLOv2. The localized images are passed toMcCulloch'sKapur entropy method to segment actual tumor region. Finally, the proposed technique is validated on three benchmark databases BRATS 2018, BRATS 2019, and BRATS 2020 for tumor detection. The proposed method achieved greater than 0.90 prediction scores in localization, segmentation and classification of brain lesions. Moreover, classification and segmentation outcomes are superior as compared to existing methods.

scholarly journals Cinematic rendering of a burst sagittal suture caused by an occipito-frontal gunshot wound

2021 ◽  
Author(s):  
Dominic Gascho ◽  
Michael J. Thali ◽  
Rosa M. Martinez ◽  
Stephan A. Bolliger
Keyword(s):  
Gunshot Wound ◽  
Three Dimensional ◽  
The Novel ◽  
Sagittal Suture ◽  
Resonance Imaging ◽  
Cinematic Rendering ◽  
Reconstruction Methods ◽  
Dimensional Reconstruction ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

AbstractThe computed tomography (CT) scan of a 19-year-old man who died from an occipito-frontal gunshot wound presented an impressive radiating fracture line where the entire sagittal suture burst due to the high intracranial pressure that arose from a near-contact shot from a 9 mm bullet fired from a Glock 17 pistol. Photorealistic depictions of the radiating fracture lines along the cranial bones were created using three-dimensional reconstruction methods, such as the novel cinematic rendering technique that simulates the propagation and interaction of light when it passes through volumetric data. Since the brain had collapsed, depiction of soft tissue was insufficient on CT images. An additional magnetic resonance imaging (MRI) examination was performed, which enabled the diagnostic assessment of cerebral injuries.

scholarly journals DJ-1 regulates the integrity and function of ER-mitochondria association through interaction with IP3R3-Grp75-VDAC1

2019 ◽  
Vol 116 (50) ◽  
pp. 25322-25328 ◽  
Author(s):  
Yi Liu ◽  
Xiaopin Ma ◽  
Hisashi Fujioka ◽  
Jun Liu ◽  
Shengdi Chen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cellular Mechanism ◽  
Loss Of Function ◽  
Wild Type ◽  
Calcium Efflux ◽  
And Function ◽  
The Brain ◽  
Early Onset Parkinson’S Disease

Loss-of-function mutations in DJ-1 are associated with autosomal recessive early onset Parkinson’s disease (PD), yet the underlying pathogenic mechanism remains elusive. Here we demonstrate that DJ-1 localized to the mitochondria-associated membrane (MAM) both in vitro and in vivo. In fact, DJ-1 physically interacts with and is an essential component of the IP3R3-Grp75-VDAC1 complexes at MAM. Loss of DJ-1 disrupted the IP3R3-Grp75-VDAC1 complex and led to reduced endoplasmic reticulum (ER)-mitochondria association and disturbed function of MAM and mitochondria in vitro. These deficits could be rescued by wild-type DJ-1 but not by the familial PD-associated L166P mutant which had demonstrated reduced interaction with IP3R3-Grp75. Furthermore, DJ-1 ablation disturbed calcium efflux-induced IP3R3 degradation after carbachol treatment and caused IP3R3 accumulation at the MAM in vitro. Importantly, similar deficits in IP3R3-Grp75-VDAC1 complexes and MAM were found in the brain of DJ-1 knockout mice in vivo. The DJ-1 level was reduced in the substantia nigra of sporadic PD patients, which was associated with reduced IP3R3-DJ-1 interaction and ER-mitochondria association. Together, these findings offer insights into the cellular mechanism in the involvement of DJ-1 in the regulation of the integrity and calcium cross-talk between ER and mitochondria and suggests that impaired ER-mitochondria association could contribute to the pathogenesis of PD.

Zinc and Acrodermatitis Enteropathica

1980 ◽  
Vol 2 (3) ◽  
pp. 88-94
Keyword(s):  
Zinc Deficiency ◽  
Autosomal Recessive ◽  
Acid Metabolism ◽  
Autosomal Recessive Disease ◽  
Dna Polymerases ◽  
Clinical Manifestations ◽  
Acrodermatitis Enteropathica ◽  
Nucleic Acid Metabolism ◽  
Zinc Metalloenzymes ◽  
Rna And Dna

Mammalian zinc metalloenzymes include alkaline phosphatase. Zinc plays a crucial role in nucleic acid metabolism. RNA and DNA polymerases and thymidine kinase are zinc-dependent enzymes. Zinc deficiency in North America is most clearly seen in the disease acrodermatitis enteropathica. This is an autosomal recessive disease due to a zinc metabolic error—not well defined—which leads to zinc deficiency. Clinical manifestations include a rash around orifices, alopecia, and diarrhea. The laboratory can demonstrate hypozincemia and hypozincuria. Clinical and biochemical remission occurs with oral zinc administration.(R.H.R.)

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