The National Metabolic Biochemistry Network - MetBio.Net

The National MetabolicBiochemistry Network‘A new resource for Clinicians ’Professor Anne GreenLead ScientistRCPCH York April 2006MetBioNet

Metabolic Biochemistry

Background– Labs facing major growth/developments inInherited Metabolic Disorders and NewbornScreening– Services under pressure• increasing workload• demands for new tests• Concerns about robustness of rare, v rare tests– no manpower or training plan(retirements & succession planning)– lack or awareness of issues by others/DHMetBioNet

The Project Aims• Form a network of stakeholderlaboratories across UK– Infrastructure for Communication– Promote sharing of information– Promote common practices– Improve service to usersMetBioNet

The Project Aims• Form a network of stakeholder laboratories acrossUK– Infrastructure for Communication– Promote sharing of information– Promote common practices– Improve service to users• Address key issues– Manpower plan– Training strategy– Service provision for rare disorders– Assay directory– Develop guidelines– Quality initiativesMetBioNet

Genetics Development Project• DH project– Oct 2002 - Oct 2004(extended to April 2006)• Hosted – Birmingham Children’sHospital• Lead Scientist– 0.4 wte– A/C supportMetBioNet

The Project Outcomes• Form a network of stakeholder laboratories acrossUK– Infrastructure for Communication– Sharing of information– Promote common practices– Improve service to users• Address key issues– Manpower plan– Training strategy– Service provision for rare disorders– Assay directory– Develop guidelines– Quality initiativesMetBioNet

Service to Users• Infrastructure of Labs– Web site www.metbio.net– ContactsMetBioNet

MetBioNet Home Page

View Stakeholder Details

Service to Users• Infrastructure of Labs– Web site– Contacts• Teaching & Education• Trainers• Web resourcesMetBioNet

Training and Education

Assay Directory• Specialist metabolic tests• Each Laboratory repertoire• Contact details• Specimen needs and transportMetBioNet

Metabolic Assay Directory

Metabolic Assay Directory - Search

Guidelines• Best practice• DGH ‘problems’• ‘How to investigate’ for ----• Practical• Lead author(s)• Peer review (2)• Lead scientist/Guideline lead - editingMetBioNet

Best Practice Guidelines

Best Practice Guidelines

Best Practice GuidelinesHOW TO INVESTIGATE FOR AN IMD ?• Hypoglycaemia• Hyperammonaemia ( & sample collection )•Seizures• Neonatal Jaundice• Hydrops (Foetal & Neonatal)• Developmental DelayMetBioNet

Background• Developmental Delay5 – 10% childhood populationGlobal delay 1-3 % children < 5 years• Over 200 different biochemicaldisorders associated with DD– many areas of metabolism– large number different tests– complex & expensiveMetBioNet

Investigation of IMD• Rare to have isolated DD– IMDs more common with associatedclinical features– DD may precede onset more specificfeatures of the disease– Importance of serial assessment• Which IMDs to consider ?• Which tests to consider ?MetBioNet

Approach to Investigation• No specific clinical findings but– family history– consanguinity– failure to thrive– intermittent/episodic illnessMetBioNet

Approach to Investigation• No specific clinical findings but– family history– consanguinity– failure to thrive– intermittent/episodic illness• Specific disorder(s) suspected• Associated clinical findings– Neurological regression– Hypotonia– Seizure disorder– Hepatomegaly(+/- splenomegaly)– Eye signs– DysmorphismMetBioNet

1st line InvestigationsGlobal delay no associated findingsBLOOD• Lactate• Urate• TSH, freeT4• Urea,Na, K Ca• Ammonia• ALT,ALP, gamma GT,albumin• Creatine kinase• Amino acidsURINE• Amino acids• Organic acids• GlycosaminoglycansMetBioNet

Seizure Disorder• Sulphite ox/Molybdenumcofactor deficiency• Urate (U & P)Sulphite (U)• Biotinidase deficiency• Non ketoticHyperglycinaemia• Creatine deficiency• Biotinidase (P)• Quantitiative AAs (P & CSF)• Creatine/Creatinine (U) &specific metabolitesMetBioNet

Associated Clinical Features2nd line Tests to ConsiderHepatomegalyOrotic Acid(+/- Splenomegaly) White Cell EnzymesOligosaccharidesBile AcidsLactate,Chol,TGs,gluc profileDysmorphismMetBioNetVLCFA,plasmalogensWhite Cell Enzymes7- dehydrocholesterolCholesterol precursorsTransferrin isoforms

Associated Clinical Features2nd line Tests to ConsiderHypotoniaVLCFA (P)Biotinidase (P)Purines/PyrimidinesAcyl Carnitines (P)BiopterinsNeurotransmittersMetBioNet

Future Plans• More Guidelines/Dissemination of GuidelinesMetBioNet

Guidelines in Progress• SUDI ( Metabolic autopsy)• Lactic Acidosis• Liver dysfunction (older child)• Cardiomyopathy• Encephalopathy• Dysmorphism• Autism• Rhabdomyolysis• Unexplained tubular dysfunctionMetBioNet

Future Plans• More Guidelines/Dissemination of Guidelines• Assay Directory• Disorder links• Links to UKGTN ( molecular tests)• European links for rarer tests• Service issues– Very rare tests– Specialised skills– Newborn screening– National clinical networks ( National review)MetBioNet

Summary – The Resource• Network of Labs– Contacts– Test repertoire• Support to clinicians– Assay directory– Guidelineswww.Metbio.net

Acknowledgements•Association of Clinical Biochemists (Training Committee)•Royal College Pathologists (SAC Clin Biochem & Genetics)•British Inherited Metabolic Disease Group•Birmingham Children’s Hospital•Genetics colleagues•Department of Health