A5066675774- Metabolism and Genetic Disorders
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Glycogen Storage Diseases and Myoclonus
- Neonatal Health and Biochemistry
- Diet and metabolism studies
- Genomics and Rare Diseases
- Biochemical and Molecular Research
- Folate and B Vitamins Research
- Amino Acid Enzymes and Metabolism
- Trypanosoma species research and implications
- Child Nutrition and Feeding Issues
- Cystic Fibrosis Research Advances
- Epilepsy research and treatment
- Fetal and Pediatric Neurological Disorders
- Diabetes and associated disorders
- Neurogenetic and Muscular Disorders Research
- Carbohydrate Chemistry and Synthesis
- Autoimmune and Inflammatory Disorders Research
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Peptidase Inhibition and Analysis
- Neonatal and fetal brain pathology
- Renal Diseases and Glomerulopathies
- Studies on Chitinases and Chitosanases
University College London
2014-2023
Great Ormond Street Hospital
2014-2023
Great Ormond Street Hospital for Children NHS Foundation Trust
2014-2021
Center for Children
2021
Wellcome Centre for Mitochondrial Research
2021
Children's Hospital Foundation
2021
William Harvey Research Institute
2021
National Institute for Health Research
2021
University of Birmingham
2021
National Hospital for Neurology and Neurosurgery
2021
<b><i>Background:</i></b> Respiratory chain (RC) disorders are clinically, biochemically, and molecularly heterogeneous. The lack of standardized diagnostic criteria poses difficulties in evaluating methodologies. <b><i>Objective:</i></b> To assess proposed adult RC that classify patients into “definite,” “probable,” or “possible” categories. <b><i>Methods:</i></b> authors applied the retrospectively to 146 consecutive children referred for investigation a suspected disorder. Data were...
The U.K. 100,000 Genomes Project is in the process of investigating role genome sequencing patients with undiagnosed rare diseases after usual care and alignment this research health implementation National Health Service. Other parts project focus on cancer infection.
<b><i>Objective:</i></b> To define the spectrum of clinical and biochemical features in 51 children with isolated complex I deficiency. <b><i>Background:</i></b> Mitochondrial respiratory chain defects are one most commonly diagnosed inborn errors metabolism. Until recently there have been technical problems diagnosis defects, is a lack information about this underreported cause dysfunction. <b><i>Methods:</i></b> A retrospective review laboratory findings was undertaken all patients who had...
Ketoacidosis is a potentially lethal condition caused by the imbalance between hepatic production and extrahepatic utilization of ketone bodies. We performed exome sequencing in patient with recurrent, severe ketoacidosis identified homozygous frameshift mutation gene encoding monocarboxylate transporter 1 (SLC16A1, also called MCT1). Genetic analysis 96 patients suspected having ketolytic defects yielded seven additional inactivating mutations MCT1, both heterozygous. Mutational status was...
To avoid potentially severe outcomes, phenylketonuria (PKU) must be detected as soon possible after birth and managed with life-long treatment. A questionnaire-based survey was performed to document diagnosis management practices for PKU in a region of Southern Eastern Europe. Prevalence data were obtained from 37/59 (63 %) centres within 19/22 (86 contacted countries (N = 8600 patients). The main results' analysis based on completed questionnaires 31 (53 15 (68 %). median 10 % patients per...
Abstract Objectives This UK‐wide study defines the natural history of argininosuccinic aciduria and compares long‐term neurological outcomes in patients presenting clinically or treated prospectively from birth with ammonia‐lowering drugs. Methods Retrospective analysis medical records prior to March 2013, then prospective until December 2015. Blinded review brain MRIs. ASL genotyping. Results Fifty‐six were defined as early‐onset ( n = 23) if symptomatic < 28 days age, late‐onset later,...
Hypertrophic cardiomyopathy (HCM) is frequently fatal in infancy. Mitochondrial disease causing infantile HCM characterised by extreme biochemical and genetic heterogeneity, but deficiency of respiratory chain complex I observed relatively frequently. Identification the precise basis has prognostic implications for likelihood neurological involvement.The authors' objective to report two heterozygous missense mutations NDUFAF1 gene as a cause patient with isolated deficiency.The authors...
The generalised form of epimerase deficiency galactosaemia has been described in only two children from unrelated families. Their progress is reported and three other affected these families are described. initial presentation was similar to classic galactosaemia. Despite treatment all have shown poor growth moderate learning difficulties. Three sensorineural deafness four pronounced dysmorphic features. older female patients normal pubertal development.
ABSTRACT Nuclear‐encoded disorders of mitochondrial translation are clinically and genetically heterogeneous. Genetic causes include defects aminoacyl‐tRNA synthetases, factors required for initiation, elongation termination protein synthesis as well ribosome recycling. We report on a new case myopathy, lactic acidosis sideroblastic anemia (MLASA) syndrome caused by defective tyrosyl aminoacylation. The patient presented at 1 year with initially attributed to iron deficiency. Bone marrow...
Sanfilippo syndrome type A (mucopolysaccharidosis IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate central nervous system and associated with progressive neurodegeneration early childhood. We report on efficacy, pharmacokinetics, safety, tolerability intrathecal (IT) administration recombinant human HNS (rhHNS) from phase IIb randomized open-label trial. Twenty-one patients, 1:1:1 to rhHNS IT 45 mg administered...
Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism (OMIM 261600). Treatment with a low-phenylalanine diet following early ascertainment by newborn screening prevents impaired cognitive development, the major disease phenotype in PKU. The overall birth prevalence PKU European, Chinese and Korean populations approximately 1/10,000. Since human PAH locus contains PKU-causing alleles polymorphic core haplotypes that describe corroborate out-of-Africa range expansion...
Neurometabolic disorders are markedly heterogeneous, both clinically and genetically, characterized by variable neurological dysfunction accompanied suggestive neuroimaging or biochemical abnormalities. Despite early specialist input, delays in diagnosis appropriate treatment initiation common. Next-generation sequencing approaches still have limitations but already enabling earlier more efficient diagnoses these patients. We designed a gene panel targeting 614 genes causing inborn errors of...