keyword
MENU ▼
Read by QxMD icon Read
search

Tyrosinemia

keyword
https://www.readbyqxmd.com/read/29787760/in-vivo-gene-correction-with-targeted-sequence-substitution-through-microhomology-mediated-end-joining
#1
Jeong Hong Shin, Soobin Jung, Suresh Ramakrishna, Hyongbum Henry Kim, Junwon Lee
Genome editing technology using programmable nucleases has rapidly evolved in recent years. The primary mechanism to achieve precise integration of a transgene is mainly based on homology-directed repair (HDR). However, an HDR-based genome-editing approach is less efficient than non-homologous end-joining (NHEJ). Recently, a microhomology-mediated end-joining (MMEJ)-based transgene integration approach was developed, showing feasibility both in vitro and in vivo. We expanded this method to achieve targeted sequence substitution (TSS) of mutated sequences with normal sequences using double-guide RNAs (gRNAs), and a donor template flanking the microhomologies and target sequence of the gRNAs in vitro and in vivo...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29764210/curative-ex-vivo-hepatocyte-directed-gene-editing-in-a-mouse-model-of-hereditary-tyrosinemia-type-1
#2
Caitlin VanLith, Rebekah Guthman, Clara T Nicolas, Kari Allen, Zeji Du, Dong Jin Joo, Scott L Nyberg, Joseph B Lillegard, Raymond Daniel Hickey
Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH). It has been previously shown that ex vivo hepatocyte-directed gene therapy using an integrating lentiviral vector to replace the defective Fah gene can cure liver disease in small and large animal models of HT1. In this study, we hypothesized that ex vivo hepatocyte-directed gene editing using CRISPR-Cas9 could be used to correct a mouse model of HT1, in which a single point mutation results in loss of FAH function...
May 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29741470/markers-of-cognitive-function-in-individuals-with-metabolic-disease-morquio-syndrome-and-tyrosinemia-type-iii
#3
James Blundell, Steven Frisson, Anupam Chakrapani, Shauna Kearney, Suresh Vijay, Anita MacDonald, Paul Gissen, Chris Hendriksz, Andrew Olson
We characterized cognitive function in two metabolic diseases. MPS-IVa (mucopolysaccharidosis IVa, Morquio) and tyrosinemia type III individuals were assessed using tasks of attention, language and oculomotor function. MPS-IVa individuals were slower in visual search, but the display size effects were normal, and slowing was not due to long reaction times (ruling out slow item processing or distraction). Maintaining gaze in an oculomotor task was difficult. Results implicated sustained attention and task initiation or response processing...
May 2018: Cognitive Neuropsychology
https://www.readbyqxmd.com/read/29517978/trap-seq-identifies-cystine-glutamate-antiporteras-a-driver-of-recovery-from-liver-injury
#4
Amber W Wang, Kirk J Wangensteen, Yue J Wang, Adam M Zahm, Nicholas G Moss, Noam Erez, Klaus H Kaestner
Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29507093/cas9-nickase-mediated-genome-editing-corrects-hereditary-tyrosinemia-in-rats
#5
Yanjiao Shao, Liren Wang, Nana Guo, Shengfei Wang, Lei Yang, Yajing Li, Mingsong Wang, Shuming Yin, Honghui Han, Li Zeng, Ludi Zhang, Lijian Hui, Qiurong Ding, Jiqin Zhang, Hongquan Geng, Mingyao Liu, Dali Li
Hereditary tyrosinemia type I (HTI) is a metabolic genetic disorder caused by mutation of fumarylacetoacetate hydrolase (FAH). Because of the accumulation of toxic metabolites, HTI causes severe liver cirrhosis, liver failure, and even hepatocellular carcinoma. HTI is an ideal model for gene therapy, and several strategies have been shown to ameliorate HTI symptoms in animal models. Although CRISPR/Cas9-mediated genome editing is able to correct the Fah mutation in mouse models, WT Cas9 induces numerous undesired mutations that have raised safety concerns for clinical applications...
May 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29502917/inborn-errors-of-metabolism-with-hepatopathy-metabolism-defects-of-galactose-fructose-and-tyrosine
#6
REVIEW
Didem Demirbas, William J Brucker, Gerard T Berry
The liver is one of the most essential organs in metabolism and is responsible for metabolizing a wide variety of molecules from amino acids to sugars. Although it is responsible for many essential metabolic processes, it is one of the most severely affected by metabolic disease because, in many cases, it is the first to be exposed to the toxic intermediates. The metabolism of galactose, fructose, and tyrosine involve the liver and although there are systemic findings in metabolic disease involved with these substrates, severe hepatopathy is a common presenting aspect of galactosemia, hereditary fructose intolerance, and tyrosinemia type I...
April 2018: Pediatric Clinics of North America
https://www.readbyqxmd.com/read/29480263/photophobia-accompanied-by-painful-plantar-punctate-hyperkeratotic-patches-tyrosinemia-type-2
#7
Ajay Anand Mohite, Joseph Abbott
No abstract text is available yet for this article.
March 2018: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29456978/a-case-of-tyrosinemia-type-iii-with-status-epilepticus-and-mental-retardation
#8
Reza Najafi, Neda Mostofizadeh, Mahin Hashemipour
Tyrosinemia type III is an autosomal recessive disorder caused by the deficiency of 4- hydroxyphenylpyruvate dioxygenase (4-HPPD). It is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into the urine. Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation. Only a few patients presenting with this disease have been described, and the clinical phenotype remains variable and unclear. We present a case, who was admitted to the hospital at the age of 4 months for recurrent seizures...
2018: Advanced Biomedical Research
https://www.readbyqxmd.com/read/29417439/antioxidants-reverse-the-changes-in-the-cholinergic-system-caused-by-l-tyrosine-administration-in-rats
#9
Lara M Gomes, Giselli Scaini, Milena Carvalho-Silva, Maria L Gomes, Fernanda Malgarin, Luiza W Kist, Maurício R Bogo, Eduardo Pacheco Rico, Alexandra I Zugno, Pedro F P Deroza, Gislaine Z Réus, Airam B de Moura, João Quevedo, Gustavo C Ferreira, Patrícia F Schuck, Emilio L Streck
Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in the activity of the enzyme tyrosine aminotransferase, leading to tyrosine accumulation in the body. Although the mechanisms involved are still poorly understood, several studies have showed that higher levels of tyrosine are related to oxidative stress and therefore may affect the cholinergic system. Thus, the aim of this study was to investigate the effects of chronic administration of L-tyrosine on choline acetyltransferase activity (ChAT) and acetylcholinesterase (AChE) in the brain of rats...
February 7, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29360903/richner-hanhart-syndrome-tyrosinemia-type-ii
#10
LETTER
Fanny Locatelli, Eve Puzenat, Jean B Arnoux, Dominique Blanc, Francois Aubin
No abstract text is available yet for this article.
December 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29348399/insulin-like-growth-factor-2-is-a-key-mitogen-driving-liver-repopulation-in-mice
#11
Min-Jun Wang, Fei Chen, Qing-Gui Liu, Chang-Cheng Liu, Hao Yao, Bing Yu, Hai-Bin Zhang, He-Xin Yan, Yibiao Ye, Tao Chen, Kirk J Wangensteen, Xin Wang, Yi-Ping Hu, Zhi-Ying He
Hepatocyte transplantation holds great promise as an alternative to orthotopic organ transplantation in the treatment of liver diseases. However, obtaining clinically meaningful levels of liver repopulation has not been achieved because the mechanisms regulating hepatocyte proliferation in recipient livers have not yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I, the fumarylacetoacetate hydrolase-deficient (Fah-/- ) mouse, we found gradually increasing expression level of insulin-like growth factor 2 (IGF2) in the hepatocytes of host livers...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29326876/mildly-elevated-succinylacetone-and-normal-liver-function-in-compound-heterozygotes-with-pathogenic-and-pseudodeficient-fah-alleles
#12
Hao Yang, Francis Rossignol, Denis Cyr, Rachel Laframboise, Shu Pei Wang, Jean-François Soucy, Marie-Thérèse Berthier, Yves Giguère, Paula J Waters, Grant A Mitchell
Background: A high level of succinylacetone (SA) in blood is a sensitive, specific marker for the screening and diagnosis of hepatorenal tyrosinemia (HT1, MIM 276700). HT1 is caused by mutations in the FAH gene, resulting in deficiency of fumarylacetoacetate hydrolase. HT1 newborns are usually clinically asymptomatic, but have coagulation abnormalities revealing liver dysfunction. Treatment with nitisinone (NTBC) plus dietary restriction of tyrosine and phenylalanine prevents the complications of HT1...
March 2018: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/29259521/nuclease-mediated-gene-therapies-for-inherited-metabolic-diseases-of-the-liver
#13
REVIEW
Taylor E Bryson, Caitlin M Anglin, P Hudson Bridges, Renee N Cottle
Inherited metabolic diseases (IMDs) of the liver represent a vast and diverse group of rare genetic diseases characterized by the loss or dysfunction of enzymes or proteins essential for metabolic pathways in the liver. Conventional gene therapy involving adeno-associated virus (AAV) serotype 8 vectors provide therapeutically high levels of hepatic transgene expression facilitating the correction of the disease phenotype in pre-clinical studies and are currently being evaluated in clinical trials for multiple IMDs...
December 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/29201126/neurological-crises-after-discontinuation-of-nitisinone-ntbc-treatment-in-tyrosinemia
#14
Naser Honar, Nader Shakibazad, Zahra Serati Shirazi, Seyed Mohsen Dehghani, Soroor Inaloo
Objective: Tyrosinemia type 1 is a hereditary disorder with liver, kidney and nervous system involvement. Neurological crises can occur in tyrosinemic patients without treatment or when treatment stops. Here we report three children that developed diaphragmatic paralysis after discontinuation of nitisinone. In patients with tyrosinemia type 1, combined treatment with nitisinone and a low-tyrosine diet have prevented neurological crises. The purpose of this article was to express the importance of taking nitisinone (NTBC) for tyrosinemia diseases and risks of inadvertent discontinuation...
2017: Iranian Journal of Child Neurology
https://www.readbyqxmd.com/read/29195145/simultaneous-quantification-of-succinylacetone-and-nitisinone-for-therapeutic-drug-monitoring-in-the-treatment-of-tyrosinemia-type-1
#15
Jonas Sundberg, Flemming Wibrand, Allan Meldgaard Lund, Mette Christensen
We present a straightforward and robust method for simultaneous quantification of succinylacetone and nitisinone in plasma using LC-ESI-MS/MS. The method has been developed for routine therapeutic drug monitoring in hepatorenal tyrosinemia type 1 (HT1) patients undergoing nitisinone treatment. Previous methods are based on separate analyses of succinylacetone and nitisinone, often using the potentially harmful compound hydrazine for derivatization of the former. In the present procedure, succinylacetone is derivatized in a single-step using butanolic HCl...
January 1, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29170874/daily-variation-of-ntbc-and-its-relation-to-succinylacetone-in-tyrosinemia-type-1-patients-comparing-a-single-dose-to-two-doses-a-day
#16
Nienke S Kienstra, Hannah E van Reemst, Willem G van Ginkel, Anne Daly, Esther van Dam, Anita MacDonald, Johannes G M Burgerhof, Pim de Blaauw, Patrick J McKiernan, M Rebecca Heiner-Fokkema, Francjan J van Spronsen
INTRODUCTION: In hereditary tyrosinemia type 1 (HT1) patients, the dose of NTBC that leads to the absence of toxic metabolites such as succinylacetone (SA) is still unknown. Therefore, the aims of this study were to investigate the variation and concentrations of 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) during the day in relation to the detection of SA, while comparing different dosing regimens. METHODS: All patients were treated with NTBC (mean 1...
March 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29110168/caregiver-quality-of-life-with-tyrosinemia-type-1
#17
Hailey Campbell, Rani H Singh, Eric Hall, Nadia Ali
Tyrosinemia type I (HT1) is an inborn error of metabolism (IEM). Current management guidelines include lifelong specialized diet and use of the orphan drug, nitisinone. This study explores the quality of life (QOL) of caregivers of children with HT1. Caregivers for 26 children with HT1 completed a questionnaire (TYR-QOL) adapted to this patient population from an existing validated QOL questionnaire (PKU-QOL). Responses were analyzed via domain scores, based on predetermined scoring guidelines. Results suggest HT1 has a moderate overall impact on caregiver QOL, with emotional aspects of the disease having the greatest impact...
November 6, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/29094226/aminoacidopathies-prevalence-etiology-screening-and-treatment-options
#18
REVIEW
Muhammad Wasim, Fazli Rabbi Awan, Haq Nawaz Khan, Abdul Tawab, Mazhar Iqbal, Hina Ayesha
Inborn errors of metabolism (IEMs) are a group of inherited metabolic disorders which are caused by mutations in the specific genes that lead to impaired proteins or enzymes production. Different metabolic pathways are perturbed due to the deficiency or lack of enzymes. To date, more than 500 IEMs have been reported with most of them being untreatable. However, fortunately 91 such disorders are potentially treatable, if diagnosed at an earlier stage of life. IEMs have been classified into different categories and one class of IEMs, characterized by the physiological disturbances of amino acids is called as aminoacidopathies...
April 2018: Biochemical Genetics
https://www.readbyqxmd.com/read/29039163/-screening-for-amino-acid-metabolic-disorders-of-newborns-in-zhejiang-province-prevalence-outcome-and-follow-up
#19
Xinwen Huang, Yu Zhang, Fang Hong, Jing Zheng, Jianbin Yang, Fan Tong, Huaqing Mao, Xiaolei Huang, Xuelian Zhou, Rulai Yang, Zhengyan Zhao
OBJECTIVE: To analyze the result and follow-up data of screening for newborn amino acid metabolic disorders in Zhejiang province. METHODS: A total of 1 861 262 newborns were screened for amino acid metabolic disorders during January 2009 and December 2016 in Zhejiang province. The screening results and the follow-up data were analyzed retrospectively. RESULTS: One hundred and sixty four cases were diagnosed as amino acid metabolic disorders with a prevalence of 1:11 349, including 83 with hyperphenylalaninaemia (1:22 400), 29 with neonatal intrahepatic cholestasis caused by citrin deficiency (1:64 138), 16 with methionine S-adenosyltransferase deficiency (1:116 250), 9 with maple syrup urine disease (1:206 667), 8 with argininemia (1:232 500), 7 with citrullinemia type Ⅰ (1:265 700), 6 with hyperprolinemia type Ⅰ (1:310 000), and 2 with carbamylphosphate synthetase Ⅰ deficiency(1:930 000)...
May 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28987047/-epidemiology-and-risk-factors-of-hepatocellular-carcinoma
#20
REVIEW
Agnieszka Budny, Piotr Kozłowski, Marzena Kamińska, Małgorzata Jankiewicz, Agnieszka Kolak, Bożena Budny, Witold Budny, Joanna Niemunis-Sawicka, Grzegorz Szczypiór, Bartosz Kurniawka, Franciszek Burdan
Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as α1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p...
September 29, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
keyword
keyword
11452
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"