A5049732192- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Genomics and Rare Diseases
- Diet and metabolism studies
- Folate and B Vitamins Research
- Nutrition and Health in Aging
- Amino Acid Enzymes and Metabolism
- Urinary Bladder and Prostate Research
- RNA modifications and cancer
- RNA regulation and disease
- Gut microbiota and health
- Kidney Stones and Urolithiasis Treatments
- Health and Well-being Studies
- Cerebral Palsy and Movement Disorders
- RNA Research and Splicing
- Metalloenzymes and iron-sulfur proteins
- Ectopic Pregnancy Diagnosis and Management
- Autoimmune and Inflammatory Disorders Research
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
Wellcome Centre for Mitochondrial Research
2015-2024
Newcastle University
2015-2024
Newcastle upon Tyne Hospitals NHS Foundation Trust
2018-2024
NIHR Newcastle Biomedical Research Centre
2021-2022
Royal Victoria Infirmary
2018-2021
Clinical Research Institute
2021
The Neurosciences Foundation
2015
The prevalence of mitochondrial disease has proven difficult to establish, predominantly as a result clinical and genetic heterogeneity. phenotypic spectrum expanded significantly since the original reports that associated classic syndromes with DNA (mtDNA) rearrangements point mutations. revolution in technologies allowed interrogation nuclear genome manner dramatically improved diagnosis disorders. We comprehensively assessed all forms adult include pathogenic mutations both mtDNA.Adults...
Mitochondrial disease associated with the pathogenic m.3243A>G variant is a common, clinically heterogeneous, neurogenetic disorder. Using multiple linear regression and mixed modelling, we evaluated which commonly assayed tissue (blood N = 231, urine 235, skeletal muscle 77) represents mutation load mitochondrial DNA (mtDNA) copy number most strongly burden progression. levels are correlated in blood, (R2 0.61-0.73). Blood heteroplasmy declines by ~2.3%/year; have extended previously...
Abstract In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes identify associated risk predictors. Between January 1998 June 2018, identified 111 patients with genetically determined disease who developed episodes. Post-mortem cases (n = 26) were from Newcastle Brain Tissue Resource. The primary outcome was interrogate...
Mitochondrial diseases affect >1 in 7500 live births and may be due to mutations either mitochondrial DNA (mtDNA) or nuclear (nDNA). Genetic counselling for families with diseases, especially those mtDNA mutations, provides unique difficult challenges particularly relation disease transmission prevention. We have experienced an increasing demand prenatal diagnostic testing from affected by since we first offered this service 2007. review the records of 62 samples (17 45 nDNA) analysed 2007,...
Mutations in the m.13094T>C MT-ND5 gene have been previously described three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at time analysis (median age death was 10 years (range: 5·4 months−37 years, IQR = 17·9 years). Nine manifested with LS, one mitochondrial encephalomyopathy, lactic acidosis stroke-like episodes (MELAS), Leber...
Objectives The m.3243A>G MTTL1 mutation is the most common cause of mitochondrial disease; yet there limited awareness intestinal pseudo‐obstruction (IPO) in this disorder. We aimed to determine prevalence, severity, and clinical outcome patients with m.3243A>G‐related disease manifesting IPO. Methods In large, observational cohort study, we assessed clinical, molecular, radiological characteristics genetically determined disease, who presented severe symptoms suggestive bowel...
Abnormal growth and short stature are observed in patients with mitochondrial disease, but it is unclear whether there a relationship between final adult height disease severity. To determine genetically confirmed shorter than their peers related to Analysis of relation severity as determined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS). UK Patient Cohort (Mito Cohort). 575 were identified recorded height, weight, molecular genetic diagnosis within Mito Cohort. body mass index...
Mitochondrial disease is a disorder of energy metabolism that affects 1 in 4300 adults the UK. Pregnancy associated with physiological demands have implications for metabolism. We were interested to know how pregnancy was affected women mitochondrial disease, particularly those most common pathogenic mutation m.3243A>G.Retrospective case-comparison study.Sixty-seven genetically confirmed from UK Diseases Cohort and 69 unaffected participated.Participants answered questionnaires regarding...
Primary mitochondrial disorders encompass a wide range of clinical presentations and spectrum severity. They currently lack effective disease-modifying therapies have high mortality morbidity rate. It is therefore essential to know that competitively funded research designed by academics meets the core needs people with their clinicians. Priority setting partnerships are an established collaborative methodology brings patients, carers families, charity representatives clinicians together try...
Abstract Aims Mitochondrial diseases present with a spectrum of clinical features, usually multiorgan involvement and are often characterized by loss smooth muscle function. Hence, we hypothesized that mitochondrial dysfunction may contribute to lower urinary tract (LUT) dysfunction. Methods We performed prospective cohort study at single, quaternary, disease referral center, enrolling consecutive adult patients genetically confirmed disease. Data regarding baseline characteristics burden...
Objective Regular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there limited information to guide clinical practice in conditions caused by nuclear defects. We sought determine the frequency and spectrum of abnormalities identified adult disease originated from genome. Methods Adult a genetically confirmed were followed up at national service Newcastle upon Tyne, UK (January 2009 December 2018). Case notes, molecular genetics reports,...
Providing an insight into the work of exceptional neuroscience nurses, spotlight articles give them opportunity to describe what they do and why it in detail. Here, Catherine Feeney, provides her with adults children mitochondrial disease.
People with rheumatoid arthritis (RA) are disproportionately affected by sarcopenia, the generalised loss of muscle strength and mass, consequently facing an increased risk falls, functional decline death. Currently, there no approved pharmacological treatments for sarcopenia. RA patients who start tofacitinib (a Janus kinase inhibitor) develop small increases in serum creatinine that not explained renal function changes could reflect sarcopenia improvement. The RAMUS Study is a proof...
Abstract Maternally inherited mitochondrial diseases are caused by pathogenic (mt)DNA variants. Affecting individuals at any age, they often multi-systemic and manifest extreme clinical variability. We have limited understanding of the cause this heterogeneity, which makes disease diagnosis prognosis exceptionally challenging. This is clearly demonstrated m.3243A>G, most common mtDNA variant. m.3243A>G can a severe syndrome characterised encephalomyopathy lactic acidosis stroke-like...
Objective: To better understand the demographic distribution of mitochondrial disease, phenotypic and genotypic variability progression associated with disease. Background: The heterogeneity in disease often poses a considerable diagnostic challenge to clinicians scientists. date, there are few effective treatments no known cure for disorders hence supportive care multi-disciplinary input remains fundamental element daily clinical practice. However, lack natural history makes...
<h3>Aims</h3> Mitochondrial disease refers to an immensely-diverse group of disorders with variable manifestations and age onset. Childhood-onset mitochondrial often involves multiple systems requires input from several paediatric sub-specialties. We aim determine the extra-neurological problems encountered by children genetically-confirmed diseases. Highlighting these features practicing clinicians is key providing better holistic health surveillance this debilitating multi-systemic...