metabolic research

summary

Metabolism refers to the handling of biochemical compounds in the body, such as the breakdown, transport, storage and synthesis of fats, proteins and carbohydrates as well as the production of energy from food components. Inherited metabolic disorders (IMD) affect approximately 1 in 2000 children. Severe metabolic disorders can cause impaired physical or cognitive development, neurodegenerative disease and other disabilities, as well as death in infants or children. Our research aims to enhance our understanding of the natural history of inherited disorders of metabolism and to improve diagnosis, treatment and prevention of these diseases.

group leader(s)

A/Professor Avihu Boneh
Genetic Health Services Victoria
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville Victoria 3052

group leader biography

current research projects

Project 1: Early diagnosis and natural history of patients with inherited metabolic disorders

We are studying the natural history and clinical outcomes of patients with inherited metabolic disorders, both those clinically diagnosed after presenting with signs of disease and those picked up by newborn screening. There are over 1000 patients altogether in our records. Careful collection and analysis of clinical data, including dietary details and laboratory metabolic markers, will enable a better understanding of these disorders, provide information that will be reported to parents (for example: "what to expect?") and will serve as an important step towards devising evidence-based therapies.
   
Project 2: Improving the laboratory diagnosis of inborn errors of metabolism

Mass spectrometry is a powerful technique for the identification and analysis of a wide range of biomarkers for inborn errors of metabolism. We are using it to identify new biomarkers and to develop novel, rapid screening methods for urine and blood samples from children with suspected metabolic disorders. Our vision is to develop tests that can detect the widest possible range of inborn errors of metabolism and diagnose patients in whom a specific disorder may not be clinically suspected. These tests will help us to establish earlier and more accurate diagnosis and treatment of many patients.

Project 3:  Adequacy of medically prescribed diets: Does the Protein to Energy Ratio Matter?

A significant number of children with IMD require a restriction or elimination of many 'normal' foods in their diet and, hence, the ability to provide adequate protein, energy and micronutrients remains a significant challenge. Our aim is to better understand the relationship between protein to energy intake in establishing optimal metabolic control, growth and development. We look at different biochemical markers and plan to look at the effect of these diets on gene regulation. We anticipate that this translational research will lead to evidence based safe and optimal diets prescribed to children with inborn errors of protein metabolism.

team members

• Nicole Buck - Research Officer
• Jamie Errico - Consultant
• Maureen Humphrey - PhD Student (Monash Medicine)
• Manal Ibrahim - Medical Scientist
• Joseph Karlecik - Technical Assistant
• Joy Lee - Metabolic Physician
• Erin Littlejohn - Medical Scientist
• Adriano Melino - Medical Scientists
• Sally Morrissy - Newborn Screening Nurse
• Thanh Nguyen - Medical Scientist
• Flora Pearce - Social Worker

• Nigel Pereira - MEDICAL SCIENTIST
• Heidi Peters - Metabolic Physician
• James Pitt - Head of Newborn and Metabolic Screening
• Galit Tal - Metabolic Fellow
• Maggie Tan - Medical Scientist
• Jenny Tran - MEDICAL SCIENTIST
• Lan Trieu - Medical Scientist
• Nicholas Tzanakos - Medical Scientist
• Helen Upton - Certified Genetic Counsellor
• Tyson Ware - METABOLIC FELLOW

publications

• Humphrey M., Nation J., Francis I., Boneh A. Effect of tetrahydrobiopterin on Phe/Tyr ratios and variation in Phe levels in tetrahydrobiopterin responsive PKU patients. Molecular genetics and metabolism 104 (1) : 89 - 92(2011) PubMed
• Hunter MF., Peters H., Salemi R., Thorburn D., MacKay MT. Alpers syndrome with mutations in POLG: Clinical and investigative features. Pediatric Neurology 45 (5) : 311 - 318(2011)
• Kolker S., Christensen E., Leonard JV., Greenberg CR., Boneh A., Burlina AB., Burlina AP., Dixon M., Duran M., Cazorla AG., Goodman SI., Koeller DM., Kyllerman M., Muhlhausen C., Muller E., Okun JG., Wilcken B., Hoffmann GF., Burgard P. Diagnosis and management of glutaric aciduria type I - revised recommendations. JOURNAL OF INHERITED METABOLIC DISEASE 34 (3) : 677 - 694(2011) PubMed
• Koves IH., Russo VC., Higgins S., Mishra A., Pitt J., Cameron FJ., Werther GA. An In Vitro Paradigm for Diabetic Cerebral Oedema and its Therapy: A Critical Role for Taurine and Water Channels. Neurochemical Research 37 (1) : 182 - 192(2011) PubMed

competitive funding

Murdoch Childrens Research Institute

collaborations & affiliations

Prof. Vicki Anderson, Critical Care and Neurosciences Theme, MCRI
Prof. Helen Truby, Department of Nutrition and Dietetics, Monash University
Dr Jeff Craig, Environment Genes and Health, MCRI