Main Interests/Achievements
We have made significant contributions to the elucidation of the following inborn errors and their treatment (the numbers in brackets are the reference numbers in the Online Mendelian Inheritance in Man [OMIM] database, http://www.ncbi.nlm.nih.gov/omim)
- Disorders of bile acid synthesis - some treatable by bile acid replacement therapy (607764, 604741, 213700, 604489, 261515, 603711)
- Peroxisomal disorders (excluding disorders already mentioned) - biogenesis disorders (e.g. 603360), and disorders of plasmalogen synthesis (602744)
- Disorders of monoamine neurotransmitter synthesis causing infantile Parkinsonism - treatable in some cases (608643, 191290)
- Disorders of fatty acid oxidation - detectable by newborn screening with treatment available to prevent brain damage (201450) or as cause of hyperisulinism treatable with diazoxide (609975)
- Disorders of cholesterol synthesis causing developmental delay and malformations (270400, 602398, 302960, 215140)
- Disorders leading to phytosterol accumulation - both genetic (210520) and as a consequence of parenteral nutrition, the latter leading to severe liver disease and treatable by reduction of phytosterol intake.
- Congenital disorders of glycosylation (212065, 608104, 611908)
- Disorders affecting vitamin B6 metabolism causing B6-responsive epilepsy (610090, 107323)
- Disorders of manganese transport causing dystonia / Parkinsonism and chronic liver disease (611146) - treatable with disodium calcium edetate and iron supplementation
- Disorders of intermediary metabolism causing movement disorders e.g. pyruvate dehydrogenase E2 deficiency (245348) treatable with a ketogenic diet and hydroxyisobutyryl-CoA hydrolase deficiency (610690)
Grants
Principal Investigator
Great Ormond Street Children's Charity
- 2010 - 2012: W1228 Metabolic Research. £118,052
- 2011 - 2012: W1022 Vitamin B6 metabolism in neonates and the effect of feeding method. £86,442
- 2012 - 2014: W1216 Identification of children whose epilepsy can be controlled better by vitamin B6 than anti-epileptic drugs. £53,386
- 2012 - 2015: W1254 Inborn Errors of Metabolism / Other Novel Therapeutic Interventions. /3197,085
Donation from Parents of a Child with a Metabolic Disorder
- 2010 - 2011: Measurement of S2-carboxylpropylcysteamine in urine and use in treatment of 3-hydroxyisobutyryl-CoA hydrolase deficiency. £31,000
Industry Sponsored Investigator Led Project
- 2012 - 2015: Actelion UK Ltd. Tests for diagnosis and monitoring of Niemann-Pick C disease. £72,500
Co-Applicant
NIHR Biomedical Research Centre
- 2009 - 2012: Is pyridox(am)ine phosphate oxidase deficiency a common cause of epilepsy, infertility, miscarriage and premature birth? BRC Senior Postdoctoral Personal Fellowship for Dr P. Mills. £104,612
European Union
- 2012 - 2015: Innovative medicine initiative EU Consortium - Stem cells for biological assays of novel drugs and predictive toxicology (StemBANcc). 850,000 Euros
- 2013 - 2016: European Union SME Targetive collaborative. Health and the understanding of metabolism, aging and nutrition (HUMAN) project. 613,000 Euros
Action Medical Research
- 2012 - 2015: Investigation of manganese metabolism and treatment development for neurological childhood disorders associated with manganese accumulation using a zebrafish gene knockout model. Research Training Fellowship for Dr. Karin Tuschl. £200,000