keyword
https://read.qxmd.com/read/32936663/clinical-utilization-of-dried-blood-spot-nitisinone-ntbc-and-succinylacetone-sa-concentrations-in-hereditary-tyrosinaemia-type-1-a-uk-centre-experience
#21
JOURNAL ARTICLE
Mildrid Yeo, Charles Turner, Neil R Dalton, Yusof Rahman, Roshni Vara
BACKGROUND: Dried blood spot monitoring of nitisinone and succinylacetone in hereditary tyrosinaemia type 1 patients is not widely available in the United Kingdom. Currently, biochemical monitoring utilizes urinary succinylacetone, blood spot tyrosine and phenylalanine monitoring, which can lack in convenience and accuracy, respectively. METHODS: We report the development of a dried blood spot assay for nitisinone and succinylacetone and analysed retrospective clinical and biochemical data for hereditary tyrosinaemia type 1 patients from a single UK centre...
November 2020: Annals of Clinical Biochemistry
https://read.qxmd.com/read/32820610/severe-neurological-crisis-in-adult-patients-with-tyrosinemia-type-1
#22
Charlotte Dawson, Radha Ramachandran, Samreen Safdar, Elaine Murphy, Orlando Swayne, Jonathan Katz, Philip N Newsome, Tarekegn Geberhiwot
We report six adult patients with Tyrosinaemia type 1 (HT-1) who presented with recurrent porphyria-like neurological crises after discontinuation/interruption of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) treatment. The crises were life-threatening for some of the patients, with respiratory muscle paralysis requiring ventilatory support, hemodynamic disturbance due to autonomic changes requiring resuscitation, acute progressive ascending motor neuropathy causing profound impairment, recurrent seizures, and neuropathic pain...
September 2020: Annals of Clinical and Translational Neurology
https://read.qxmd.com/read/32325917/natural-protein-tolerance-and-metabolic-control-in-patients-with-hereditary-tyrosinaemia-type-1
#23
JOURNAL ARTICLE
Ozlem Yilmaz, Anne Daly, Alex Pinto, Catherine Ashmore, Sharon Evans, Girish Gupte, Saikat Santra, Mary Anne Preece, Patrick Mckiernan, Steve Kitchen, Nurcan Yabanci Ayhan, Anita MacDonald
In a longitudinal retrospective study, we aimed to assess natural protein (NP) tolerance and metabolic control in a cohort of 20 Hereditary Tyrosinaemia type I (HTI) patients. Their median age was 12 years ([3.2-17.7 years], n = 11 female, n = 8 Caucasian, n = 8 Asian origin, n = 2 Arabic and n = 2 Indian). All were on nitisinone (NTBC) with a median dose of 0.7 g/kg/day (range 0.4-1.5 g/kg/day) and were prescribed a tyrosine (Tyr)/phenylalanine (Phe)-restricted diet supplemented with Tyr/Phe-free L-amino acids...
April 19, 2020: Nutrients
https://read.qxmd.com/read/32083330/nitisinone-causes-acquired-tyrosinosis-in-alkaptonuria
#24
JOURNAL ARTICLE
Milad Khedr, Maggie S Cooper, Andrew T Hughes, Anna M Milan, Andrew S Davison, Brendan P Norman, Hazel Sutherland, Jonathan C Jarvis, Richard Fitzgerald, Louise Markinson, Eftychia-Eirini Psarelli, Parisa Ghane, Nicolaas E P Deutz, James A Gallagher, Lakshminarayan R Ranganath
For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy as a disease modifying agent. NTBC-induced hypertyrosinaemia has been associated with cognitive impairment and potentially sight-threatening keratopathy. In the context of a non-lethal condition (ie, AKU), these serious risks call for an evaluation of the wider impact of NTBC on the tyrosine pathway...
September 2020: Journal of Inherited Metabolic Disease
https://read.qxmd.com/read/31937937/correcting-tyrosinaemia-via-a-point-mutation
#25
COMMENT
Kiran Musunuru
No abstract text is available yet for this article.
January 2020: Nature Biomedical Engineering
https://read.qxmd.com/read/31740768/adenine-base-editing-in-an-adult-mouse-model-of-tyrosinaemia
#26
JOURNAL ARTICLE
Chun-Qing Song, Tingting Jiang, Michelle Richter, Luke H Rhym, Luke W Koblan, Maria Paz Zafra, Emma M Schatoff, Jordan L Doman, Yueying Cao, Lukas E Dow, Lihua Julie Zhu, Daniel G Anderson, David R Liu, Hao Yin, Wen Xue
In contrast to traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here we show in a mouse model of tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (FAH)-positive hepatocytes in the liver, and rescued weight loss in mice...
January 2020: Nature Biomedical Engineering
https://read.qxmd.com/read/31503358/dietary-restriction-of-tyrosine-and-phenylalanine-lowers-tyrosinemia-associated-with-nitisinone-therapy-of-alkaptonuria
#27
JOURNAL ARTICLE
Juliette H Hughes, Peter J M Wilson, Hazel Sutherland, Shirley Judd, Andrew T Hughes, Anna M Milan, Jonathan C Jarvis, George Bou-Gharios, Lakshminarayan R Ranganath, James A Gallagher
Alkaptonuria (AKU) is caused by homogentisate 1,2-dioxygenase deficiency that leads to homogentisic acid (HGA) accumulation, ochronosis and severe osteoarthropathy. Recently, nitisinone treatment, which blocks HGA formation, has been effective in AKU patients. However, a consequence of nitisinone is elevated tyrosine that can cause keratopathy. The effect of tyrosine and phenylalanine dietary restriction was investigated in nitisinone-treated AKU mice, and in an observational study of dietary intervention in AKU patients...
March 2020: Journal of Inherited Metabolic Disease
https://read.qxmd.com/read/30926434/direct-infusion-based-metabolomics-unveils-biochemical-profiles-of-inborn-errors-of-metabolism-in-cerebrospinal-fluid
#28
JOURNAL ARTICLE
Hanneke A Haijes, Maria van der Ham, Johan Gerrits, Peter M van Hasselt, Hubertus C M T Prinsen, Monique G M de Sain-van der Velden, Nanda M Verhoeven-Duif, Judith J M Jans
BACKGROUND: For inborn errors of metabolism (IEM), metabolomics is performed for three main purposes: 1) development of next generation metabolic screening platforms, 2) identification of new biomarkers in predefined patient cohorts and 3) for identification of new IEM. To date, plasma, urine and dried blood spots are used. We anticipate that cerebrospinal fluid (CSF) holds additional - valuable - information, especially for IEM with neurological involvement. To expand metabolomics to CSF, we here tested whether direct-infusion high-resolution mass spectrometry (DI-HRMS) based non-quantitative metabolomics could correctly capture the biochemical profile of patients with an IEM in CSF...
May 2019: Molecular Genetics and Metabolism
https://read.qxmd.com/read/30904888/unusual-first-presentation-of-a-metabolic-disorder
#29
JOURNAL ARTICLE
Claire Emma Strauss, Gayle Hann
An 8-month-old boy presented to hospital with a fever, irritability and 'back arching'. On examination, he demonstrated profound opisthotonic posturing and had tonsillitis. He had a full septic screen and was treated with broad spectrum antibiotics. Blood tests showed a transaminitis, raised alpha fetoprotein and deranged clotting. The clotting abnormalities and raised alpha fetoprotein persisted post discharge and an abdominal ultrasound showed steatosis, splenomegaly and bilateral increased renal cortical reflectivity...
March 22, 2019: BMJ Case Reports
https://read.qxmd.com/read/29527263/homologous-recombination-mediates-stable-fah-gene-integration-and-phenotypic-correction-in-tyrosinaemia-mouse-model
#30
JOURNAL ARTICLE
Norman Junge, Qinggong Yuan, Thu Huong Vu, Simon Krooss, Christien Bednarski, Asha Balakrishnan, Toni Cathomen, Michael P Manns, Ulrich Baumann, Amar Deep Sharma, Michael Ott
AIM: To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout ( Fah -/-) mice by homologous-recombination-mediated targeted addition of the Fah gene. METHODS: C57BL/6 Fah∆exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah cDNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms (620 bp and 749 bp long) of the Rosa26 gene locus...
February 27, 2018: World Journal of Hepatology
https://read.qxmd.com/read/29497141/the-somatic-fah-c-1061c-a-change-counteracts-the-frequent-fah-c-1062-5g-a-mutation-and-permits-u1snrna-based-splicing-correction
#31
JOURNAL ARTICLE
Daniela Scalet, Claudia Sacchetto, Francesco Bernardi, Mirko Pinotti, Stan F J van de Graaf, Dario Balestra
In tyrosinaemia type 1(HT1), a mosaic pattern of fumarylacetoacetase (FAH) immunopositive or immunonegative nodules in liver tissue has been reported in many patients. This aspect is generally explained by a spontaneous reversion of the mutation into a normal genotype. In one HT1 patient carrying the frequent FAH c.1062+5G>A mutation, a second somatic change (c.1061C>A) has been reported in the same allele, and found in immunopositive nodules. Here, we demonstrated that the c.1062+5G>A prevents usage of the exon 12 5' splice site (ss), even when forced by an engineered U1snRNA specifically designed on the FAH 5'ss to strengthen its recognition...
May 2018: Journal of Human Genetics
https://read.qxmd.com/read/29371734/haemophagocytic-lymphohistiocytosis-in-a-preterm-infant-a-case-report
#32
JOURNAL ARTICLE
Na Mi Lee, Dae Yong Yi, Shin Weon Yoon, Soo Ahn Chae, In Seok Lim, Yong Sung Choi
Haemophagocytic lymphohistiocytosis (HLH) is a rare disease with a sepsis-like progression that leads to multiple organ dysfunction syndrome, especially in preterm infants. We present herein a case of HLH in a premature infant presenting with disseminated intravascular coagulopathy (DIC) and liver failure. A male infant, with weight 810g and delivered at the gestational age of 25 weeks and 2 days, was misdiagnosed with tyrosinaemia for several weeks. He presented with anaemia, thrombocytopaenia, persistent DIC, and elevated liver enzymes despite continuous transfusion and broad-spectrum antibiotics...
January 2018: JPMA. the Journal of the Pakistan Medical Association
https://read.qxmd.com/read/29143197/three-cases-of-hereditary-tyrosinaemia-type-1-neuropsychiatric-outcomes-and-brain-imaging-following-treatment-with-ntbc
#33
JOURNAL ARTICLE
Helen Walker, Mervi Pitkanen, Yusof Rahman, Sally F Barrington
AIM: To examine neuropsychiatric outcomes in adults with hereditary tyrosinaemia type I (HT-1), treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) and correlate these with functional imaging as well as with tyrosine and phenylalanine-tyrosine (Phe:Tyr) ratios. DESIGN: We retrospectively reviewed the medical records of three adult HT-1 patients with a particular focus on their FDG PET/CT brain scans, neuropsychiatric assessment (including neurocognitive assessment and mood and anxiety ratings) as well as mean tyrosine and phenylalanine levels and Phe:Tyr ratios for 3-month period...
2018: JIMD Reports
https://read.qxmd.com/read/28755195/from-weed-killer-to-wonder-drug
#34
REVIEW
Edward A Lock
The discovery that a natural product leptospermone had herbicidal activity formed the starting point for chemical synthesis to find more activity and selectivity. A series of molecules called triketones were found to possess good activity and 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) was selected for toxicology testing. NTBC fed at low doses to rats and dogs caused keratopathy, which on cessation of the diet recovered. Mice, rabbits and monkeys fed NTBC did not show this response. Research discovered that NTBC caused tyrosinaemia which was due to inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase in both mammals and plants thereby finding a novel target for killing plants...
2017: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/28755190/diagnosing-hepatorenal-tyrosinaemia-in-europe-newborn-mass-screening-versus-selective-screening
#35
REVIEW
Anibh M Das, Sebene Mayorandan, Nils Janzen
Hepatorenal tyrosinaemia (HT1) is a serious condition that used to be fatal before the advent of nitisinone (NTBC, Orfadine®) as a therapeutic option. We have recently shown that selective screening is inadequate as initial symptoms are often uncharacteristic which leads to a considerable delay in diagnosis and treatment. This has a negative impact on morbidity and mortality as well as long-term outcome. For example, the odds ratio to develop hepatocellular carcinoma is 12.7 when treatment is initiated after the first birthday compared to start of treatment in the neonatal period...
2017: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/28755186/liver-transplantation-for-hereditary-tyrosinaemia-type-1-in-the-united-kingdom
#36
JOURNAL ARTICLE
Patrick McKiernan
Fourteen children have undergone liver transplantation for hereditary tyrosinaemia type 1 (HT1) at Birmingham Children's hospital (BCH) since 1989; six were treated prior to the availability of Nitisinone in 1993 and eight in the post Nitisinone era. Prior to 1993 essentially all children with HT1 were referred for transplantation. In the Nitisinone era only those with unresponsive liver failure or suspected malignancy were considered for transplantation. Those who were treated pre-emptively following newborn screening have no evidence of liver disease and none have required transplantation...
2017: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/28583322/ocular-findings-in-patients-with-cholestatic-disorders-of-infancy-a-single-centre-experience
#37
JOURNAL ARTICLE
Hanaa El-Karaksy, Dalia Hamed, Hanan Fouad, Engy Mogahed, Heba Helmy, Fotouh Hasanain
BACKGROUND AND STUDY AIMS: Neonatal cholestasis can be associated with ocular findings that might aid in its diagnosis, e.g., Alagille syndrome (AGS) and Niemann Pick disease (NPD). We aimed to investigate the frequency of ocular manifestations in infants with cholestasis. PATIENTS AND METHODS: This cross-sectional study included cholestatic infants presenting to the Paediatric Hepatology Unit, Cairo University Paediatric Hospital, Cairo, Egypt. All infants underwent examination of lid, ocular motility, anterior and posterior segments and measurement of intraocular pressure, cycloplegic refraction, ocular ultrasonography and vision...
June 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://read.qxmd.com/read/27814443/type-1-tyrosinaemia
#38
JOURNAL ARTICLE
M A Mannion, A Smith, P Mayne, A A Monavari
Tyrosinaemia type 1 (TYR1, OMIM# 276700) is a rare autosomal recessive disease that results from an enzyme defect that leads to a deficiency in fumarylacetoacetase (FAH)1. We present 3 cases of TYR1 in the Irish population over a 9 year period, the only cases known to have been diagnosed in Ireland since 1989. The common presenting symptom was hypoglycaemia and the diagnosis was made by the identification of the pathognomonic biomarker succinylacetone on urine organic acid analysis. We discuss the clinical presentation, biochemical and genetic results including one novel mutation...
June 10, 2016: Irish Medical Journal
https://read.qxmd.com/read/27572891/reprogramming-metabolic-pathways-in-vivo-with-crispr-cas9-genome-editing-to-treat-hereditary-tyrosinaemia
#39
JOURNAL ARTICLE
Francis P Pankowicz, Mercedes Barzi, Xavier Legras, Leroy Hubert, Tian Mi, Julie A Tomolonis, Milan Ravishankar, Qin Sun, Diane Yang, Malgorzata Borowiak, Pavel Sumazin, Sarah H Elsea, Beatrice Bissig-Choisat, Karl-Dimiter Bissig
Many metabolic liver disorders are refractory to drug therapy and require orthotopic liver transplantation. Here we demonstrate a new strategy, which we call metabolic pathway reprogramming, to treat hereditary tyrosinaemia type I in mice; rather than edit the disease-causing gene, we delete a gene in a disease-associated pathway to render the phenotype benign. Using CRISPR/Cas9 in vivo, we convert hepatocytes from tyrosinaemia type I into the benign tyrosinaemia type III by deleting Hpd (hydroxyphenylpyruvate dioxigenase)...
August 30, 2016: Nature Communications
https://read.qxmd.com/read/27305933/predicting-tyrosinaemia-a-mathematical-model-of-4-hydroxyphenylpyruvate-dioxygenase-inhibition-by-nitisinone-in-rats
#40
JOURNAL ARTICLE
John P Ward, Joanne L Dunster, Gianne Derks, Pratibha Mistry, José D Salazar
Nitisinone or 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione is a reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme important in tyrosine catabolism. Today, nitisinone is successfully used to treat Hereditary Tyrosinaemia type 1, although its original expected role was as a herbicide. In laboratory animals, treatment with nitisinone leads to the elevation of plasma tyrosine (tyrosinaemia). In rats and Beagle dogs, repeat low-dose exposure to nitisinone leads to corneal opacities whilst similar studies in the mouse and Rhesus monkey showed no comparable toxicities or other treatment related findings...
September 1, 2017: Mathematical Medicine and Biology: a Journal of the IMA
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