BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE
BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS WEST MIDLANDS LABORATORY SERVICE FOR INHERITED METABOLIC DISORDERS BIRMINGHAM CHILDREN’S HOSPITAL HANDBOOK FOR USERS The Department of Newborn Screening and Biochemical Genetics at Birmingham Children's Hospital NHS Foundation Trust (BCH) is a CPA Accredited Laboratory which provides services for the diagnosis and monitoring of patients with Inherited Metabolic Disorders (IMD) primarily for the West Midlands. The laboratory staff are part of a wide multidisciplinary IMD team comprising clinical, nursing and dietetic staff. For general information about the Department of Newborn Screening and Biochemical Genetics and Clinical IMD services please consult the Birmingham Children's Hospital Website: http://www.bch.nhs.uk/ The purpose of this handbook is to provide information on the IMD laboratory service including test repertoire, specimen requirements and details on accessing our service. It also provides some guidance on investigating patients for suspected IMD. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 1 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Contacts - “The Team” Scientific Staff Mrs Mary Anne Preece Consultant Biochemist & Director of Laboratory IMD Amino Acids, Organic Acids, Acylcarnitines 0121 333 9940 [email protected] Dr Sarah Ball Molecular Geneticist Molecular Genetics & Antenatal Diagnoses 0121 333 9877 [email protected] Dr Tim Hutchin Senior Biochemist Storage Disorders, Cell Culture & Antenatal Diagnoses 0121 333 9902 [email protected] Mrs Linda Jenkinson (until 31/07/13) Chief Biomedical Scientist 0121 333 9942 [email protected] Mrs Sue Alger Principal Biochemist 0121 333 9941 [email protected] Dr Rachel Webster (until 02/08/13) Principal Biochemist 0121 333 9941 [email protected] Dr Adam Gerrard Senior Biochemist 0121 333 9948 [email protected] Mrs Glynis Kane Laboratory Manager 0121 333 9920 (until 31/08/13) [email protected] Dr Alison Armitage Senior Biochemist 0121 333 9948 [email protected] Consultant Metabolic Paediatricians Dr Anupam Chakrapani 0121 333 9899 [email protected] Dr Saikat Santra 0121 333 9899 [email protected] Dr Suresh Vijay 0121 333 9899 [email protected] Consultants in Metabolic Disorders (adults) Dr Tarek Hiwot Queen Elizabeth Hospital Birmingham 0121 627 1627 ext 51592 [email protected] Dr Charlotte Dawson Queen Elizabeth Hospital Birmingham 0121 627 1627 ext 51592 [email protected] Useful phone numbers: Duty Metabolic Biochemist (general clinical queries) 0121 333 9864 Duty Senior Biomedical Scientist (results) 0121 333 9942 Fax Number 0121 333 9911 IMD laboratory handbook Document ID: DOC39 Version: 5 Page 2 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS GENERAL INFORMATION Service Hours Normal Working Hours The laboratory is open for the receipt of routine samples from 09.00-17.10h Monday to Friday (except Bank Holidays). Out of Hours Service Out-of-hours analytical services are available for plasma ammonia and CSF and plasma lactate as part of the General Blood Sciences: Clinical Chemistry on-call service at BCH. No other analytical service for inborn errors of metabolism is usually available out-of-hours but, in emergency, specific tests may be provided if clinically justified and if staff are available. If analytical or advisory services are required out of hours please contact the on-call Consultant Biochemist in the first instance (via the BCH switchboard, Telephone No. 0121333 9999). Sending a Specimen Information on sending specimens collected within the Birmingham Children’s Hospital can be obtained from the Hospital Laboratory Handbook located on the Intranet. Specimens collected at hospitals outside Birmingham Children’s Hospital should, where possible, be sent via the clinical chemistry/blood sciences department in the originating hospital. In some cases specimens for certain tests may require immediate transport by courier or taxi. Specific needs are listed in the specimen requirement section of the table in the Handbook. Tissue biopsies may require transport in special tubes in the frozen state. Please contact the laboratory before sending such specimens. If using a courier or taxi please request that the specimens are delivered to the Paediatric Laboratory Medicine Block entrance at Whittall Street not to the main hospital post room. Laboratory postal address Department of Newborn Screening and Biochemical Genetics Paediatric Laboratory Medicine Birmingham Children’s Hospital Steelhouse Lane Birmingham B4 6NH IMD laboratory handbook Document ID: DOC39 Version: 5 Delivery address for specimens sent by courier Duty Scientist Department of Newborn Screening and Biochemical Genetics Paediatric Laboratory Medicine Laboratory Block Whittall Street Birmingham B4 6DH Page 3 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Request forms and minimum data set The request form must include a minimum of the following information: 1. Surname 2. Source of request ie originating hospital 3. Test requested 4. And two from a) Forename b) Date of birth c) Registration number The following information is desirable: • Forename • Date of birth • Sex • Postcode (requirement for molecular genetic tests) • NHS number • Registration number • Name of requesting consultant • Sample type • Date and time of specimen collection • Referring laboratory specimen number • Clinical details (including fasting status and current drug therapy) Specimen labelling and minimum data set The specimen must be labelled with the following information: 1. Surname 2. And two from a) Forename b) Date of birth c) Registration number d) Referring laboratory specimen number The following information is desirable: • Date and time of specimen collection • Forename • Date of birth • Sex • Sample type Note: for samples in small cryotubes, due to space constraints two patient identifiers are acceptable: surname, and one from date of birth, registration number, referring laboratory specimen number A request for a urine “metabolic screen” will normally be interpreted by the laboratory as requiring urine amino acids, organic acids and “spot tests”. However if the clinical information supplied suggests other tests could be appropriate these may be added by the Duty Metabolic Biochemist. Results will normally be returned via the local laboratory at the requesting hospital. Plasma and urine specimens are stored frozen for 3 months prior to disposal. If further tests are required, please telephone to discuss whether enough specimen is remaining and suitability for analysis. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 4 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Urgent requests can often be dealt with more quickly if there is prior discussion with the team. If your request is urgent please contact the Duty Metabolic Biochemist (0121 333 9864) Key factors affecting test performance Many factors can affect biochemical results; diurnal rhythm, exercise, fasting status, drug therapy, method of specimen collection (e.g. venous or capillary), haemolysis and biological variation. Some drugs interfere with certain analyses therefore it is helpful to provide a list of current therapy on the request form accompanying the specimen. If specimens are not stored and transported as indicated in the tables below, results of some analytes may be affected. If urine specimens show signs of deterioration a repeat specimen is usually requested because diagnostic abnormalities may not be apparent. Specimen rejection We do not analyse incorrectly or inadequately labelled specimens and/or request forms (see above). Specimens that are inadequately labelled, in the incorrect anticoagulant or preservative or are received too late after sampling will not usually be analysed and a report will be issued to this effect. If appropriate, unsatisfactory specimens will be stored with routine specimens for 3 months. High Risk Specimens We do not routinely analyse high-risk specimens without prior discussion. Please contact the Duty Metabolic Biochemist before sending any such specimens. Consent It is the responsibility of the requesting doctor to obtain consent for the specimen collection and the tests requested. It is implicit in the receipt of the request form that consent has been obtained. We never take more sample than we need to but where there is material left over after laboratory testing, it may be used for other purposes such as quality assurance or audit. Specific research is regulated by the ethics committee. Consent for the use of tissue requires that patients must be given the option to refuse permission for spare material to be used. When this occurs, each request to the laboratory must be clearly marked so that specimens are not used for other purposes. There may be specific requirements for written consent for DNA tests sent to other countries, please contact the molecular genetics laboratory for further information. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 5 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Turnaround times The turnaround times of all tests are monitored. Turnaround times quoted are the anticipated times between specimen receipt in our laboratory and reporting under normal operating conditions. Time taken for the specimen to reach the laboratory and for the report to reach the requesting clinician are not included. Where appropriate, abnormal results will be telephoned to the requesting physician. The following are the targets that we aim to achieve for routine samples:Test Amino acids (qualitative plasma) Galactosaemia screen Metabolites (3-hydroxybutyrate and free fatty acids) Urine/faecal reducing substances Acyl carnitines Biotinidase Chitotriosidase Glucose-6-phosphate dehydrogenase Plasma and white cell lysosomal enzymes Tyrosinaemia screen Urine metabolic screen (qualitative amino acids, spot tests, organic acids) White cell cystine Simple DNA tests Very long chain fatty acids, phytanate and pristanate Galactose-1-phosphate 7-dehydrocholesterol Methylmalonic acid Orotate Oxalate Glycosaminoglycans Oligosaccharides Quantitative amino acids Transferrin electrophoresis Complex DNA tests Tissue/fibroblast enzymes Target Turnaround 90% in 1 week 90% in 2 weeks 90% in 3 weeks 90% in 4 weeks 90% in 8 weeks Please enquire For requests added on subsequent to receipt of the specimen, turnaround times from date of test request will be as shown above. Work referred away The department regularly refers specimens to other specialist centres in order to provide a comprehensive diagnostic service. Most UK laboratories to which samples are referred are CPA accredited. However, many of those from Europe and around the world are either not accredited or their accreditation status is unknown. The performance of referral laboratories is routinely monitored. Where work has been done in other centres it our policy to name the centre on our laboratory report. A list of referral laboratories is given in appendix D. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 6 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS SERVICES PROVIDED We offer an advisory service about which tests are appropriate for the investigation and management of inherited metabolic disorders. We welcome discussion of patient investigation with clinicians and laboratory staff prior to sending specimens. Our test repertoire covers: 1) Postnatal Diagnosis We provide a range of metabolic, enzymological and molecular genetic tests for the diagnosis of inherited metabolic disorders. Most tests are done in house whilst some very rare tests will be sent to other specialist laboratories in the UK and abroad. 2) Monitoring of Treatment We provide a range of tests for the monitoring of treatment. 3) Antenatal Diagnosis In liaison with the Regional Genetics Laboratory and Clinical Genetics Service we act as a centre for advice on antenatal testing options for inherited metabolic disorders and coordinate sample handling and the reporting of results. We attempt the audit of all antenatal diagnoses and record and report the results on an annual basis. 4) Newborn Screening The West Midlands Newborn Screening Centre is housed within the Department of Newborn Screening and Biochemical Genetics at Birmingham Children's Hospital and provides newborn screening for congenital hypothyroidism, sickle cell disease, cystic fibrosis, medium chain acyl CoA dehydrogenase deficiency and phenylketonuria including the investigation of biopterin defects. 5) Cell Culture and Tissue Banking We have facilities and are able to provide services for tissue banking and the culture and storage of skin fibroblasts, transformed lymphoblasts, cultured chorionic villus cells and cultured amniotic fluid cells. We participate in multidisciplinary clinics and Ward Rounds:Birmingham Children’s Hospital Clinical Inherited Metabolic Disorders (Dr Anupam Chakrapani, Dr Suresh Vijay, Dr Saikat Santra). Metabolic Neurology (Dr Evangeline Wassmer). Metabolic Muscle Disorders (Dr Helen Roper, Dr Nick Davies). Paediatric Liver Metabolic Disorders (Dr Pat McKiernan). University NHS Trust Adult Liver Metabolic Disorders (Dr Phil Newsome). Adult Inherited Metabolic Disorders (Dr Tarek Hiwot, Dr Charlotte Dawson) IMD laboratory handbook Document ID: DOC39 Version: 5 Page 7 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS TEST AVAILABILITY & SAMPLE REQUIREMENTS Group Tests and Profiles Some tests will detect a wide range of disorders that produce abnormalities in the particular group of analytes eg amino acids, organic acids, acylcarnitines, mucopolysaccharides & very long chain fatty acids. This type of Group Test is often used as a first line test. In other cases we have combined tests into a profile that is aimed at detecting disorders with a particular symptom or pattern of symptoms eg hepatosplenomegaly, hereditary optic atrophy. Individual Tests We also offer tests designed to diagnose a specific disorder eg plasma 7-dehydrocholesterol (Smith-Lemli-Opitz Syndrome), α-galactosidase A (Fabry’s Disease) The volume & specimen type required and transport requirements are detailed below. If the test you require is not included in our repertoire please visit the National Metabolic Biochemistry Website:- http://www.metbio.net/metbioAssays.asp IMD laboratory handbook Document ID: DOC39 Version: 5 Page 8 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS TESTS AVAILABLE Code VB = Venous Blood, VP = Venous Plasma, S = Serum, U = Urine, BS = Blood Spot, L = Liver, SB = Skin Biopsy or Cultured Fibroblasts. METABOLITES TEST 7-Dehydrocholesterol (Smith-Lemli-Opitz Syndrome) Acyl carnitines Amino Acids (Quantitative) Amino Acids (Qualitative) Biopterins (total) Carnitine Free Fatty Acids & 3Hydroxybutyrate Galactose-1-Phosphate (Quantitative) Glycosaminoglycans (Mucopolysaccharides) Homocystine (free) SPECIMEN TYPE/VOLUME VP (1ml Heparin) or 0.5ml plasma or serum TRANSPORT Room temperature VB (Heparin 0.5ml) or VP Please send plasma AND blood and a BS spots U (2ml), VB (Heparin Store plasma and CSF frozen 0.5ml) prior to shipment. Blood stained CSF 0.5ml CSF is unsuitable for analysis. U (2ml), VP (Heparin Preferably send a fasting sample. 0.5ml) Store plasma and urine frozen prior to shipment 6x10mm BS None Send at room temperature U (0.5ml), VP (Heparin 0.5ml) VP (Fluoride-Oxalate 0.5ml) Room temperature Store plasma frozen prior to shipment Store plasma frozen prior to shipment. Please state fasting status. Whole VB (Heparin 1ml) The sample must be received within 24 hours of collection. U (5ml) Store frozen prior to shipment VP (Heparin 0.5ml) Homocysteine (total) VP 0.2 mL Methylmalonic acid (Quantitative) Mono and Disaccharides Oligosaccharides U (1 ml) VP (Heparin 1ml) U (5ml) Faeces (liquid) U (1ml) Organic Acid Analysis Orotic Acid (Quantitative) Oxalate (Oxalosis) See sulphur-containing amino acids quantitation for sample preparation. Separate within 30 minutes of collection Store frozen prior to shipment Send frozen if possible Send frozen if possible Room temperature Room temperature Room temperature Send frozen if possible Room temperature Send frozen if possible Store frozen prior to shipment Send frozen if possible Store frozen prior to shipment Send frozen if possible U (5ml) Store frozen prior to shipment Send frozen if possible U (5ml) Store frozen prior to shipment Send frozen if possible U (5ml) Acidify to pH<2 Send frozen if possible None Room temperature Store plasma frozen prior to shipment None Send at room temperature Separate within 30 minutes of collection and deproteinise immediately (Deproteinising solution available to referring hospitals on request) See above Send frozen Phenylalanine & tyrosine 2x10mm BS (monitoring) Phytanic & Pristanic acids VP (Heparin, FluorideOxalate or EDTA 1ml) Porphobilinogen Synthase VB (Heparin 0.5ml). BS , Screen (Tyrosinaemia red blood cells. Screen) Sulphur-containing Amino VB (Heparin 0.5ml) Acid Quantitative (cystine, homocystine and methionine) Sulphocysteine – please request free and total homocysteine SPECIFIC NEEDS Store plasma frozen prior to shipment See above IMD laboratory handbook Document ID: DOC39 Version: 5 Room temperature Page 9 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Transferrin Electrophoresis VP, VS 0.5 ml (Congenital Disorders of Glycosylation) Very long chain fatty acids VP (Heparin, FluorideOxalate or EDTA 2ml) White Cell Cystine VB (Heparin 5ml –for (Cystinosis) monitoring, 10ml for diagnosis) None Room temperature Store plasma frozen prior to shipment Prior arrangement essential Room temperature Send whole blood to arrive before 1pm on the day of sampling ENZYMES Individual Lysosomal Enzyme Assays (For sample requirements for enzyme profiles see below) All samples should be received in our Department within 24 hours of collection Assays are typically performed on leucocytes isolated from whole blood. For optimum yield of cells the sample needs to reach us within 24 hours of collection. The volume of blood required varies according to the number and type of tests requested. For these reasons it is important to contact the laboratory prior to taking the sample. Please do not use first or second-class post. Samples can be stored overnight at +4C - DO NOT FREEZE OR SEPARATE. Some enzymes can be measured on plasma or blood spots as an initial screen but any abnormal result would have to be confirmed on leucocytes isolated from whole blood. Unless pre-agreed we will measure plasma or DBS in the first instance. TEST Acid Esterase (Wolman’s Disease) α-N-Acetylgalactosaminidase (Schindler’s Disease) α-Galactosidase A (Fabry’s Disease) (Males only) WHOLE BLOOD VB (EDTA 5ml) - VB (EDTA 5ml) VB (EDTA 5ml) or DBS (EDTA)* - α-Fucosidase (Fucosidosis) VB (EDTA 5 ml) α-Mannosidosis (Mannosidosis) VB (EDTA 5 ml) α-Glucosidase (Acarbose inhibited) (Pompe’s Disease) Arylsulphatase A (Metachromatic Leucodystrophy) PLASMA VB (EDTA 5 ml) or DBS (EDTA)* VB (EDTA 5 ml) VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml - Aspartylglucosaminidase (Aspartylglucoaminuria) - β-Galactocerebrosidase (Krabbe’s Leucodystrophy) β-Galactosidase (GM1 Gangliosidosis) β-Glucosidase (Gaucher’s Disease) VB (EDTA 5 ml) VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml - VB (EDTA 5 ml) - VB (EDTA 5 ml) - β-Glucuronidase (Sly’s Disease, MPS VII) VB (EDTA 5 ml) β-Mannosidase (Mannosidosis) VB (EDTA 5 ml) Hexosaminidase A (Tay-Sach’s Disease) VB (EDTA 5ml) IMD laboratory handbook Document ID: DOC39 Version: 5 VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml VB (Heparin, EDTA or Page 10 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Hexosaminidase (Total) (Sandhoff’s Disease) VB (EDTA 5 ml) I-Cell Screen (Mucolipidoses II & III) - Palmitoyl Protein Thioesterase 1 (CLN1) VB (EDTA 5 ml) clotted, 0.5ml) VP/VS 0.2ml VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml - Sphingomyelinase (Niemann-Pick types A & B) VB (EDTA 5 ml) - Tripeptidyl Peptidase 1 (CLN2) VB (EDTA 5 ml) - *Samples should be taken in EDTA and either a dried blood spot (DBS) made or the whole blood sent to our laboratory where we will make a blood spot (in these cases 1ml of sample is sufficient). IMD laboratory handbook Document ID: DOC39 Version: 5 Page 11 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Cultured Fibroblast Enzymes All the above enzymes can be assayed in cultured fibroblasts. Please see the requirements for skin biopsies for culture. Filipin Staining (Niemann-Pick Type C) SB (Culture) Group Tests of Lysosomal Enzymes For each profile we require a minimum of 10 ml of venous blood in EDTA Gangliosidosis Profile Leucocyte β-galactosidase (GM1 Gangliosidosis) Leucocyte total hexosaminidase (Sandhoff’s disease) Leucocyte hexosaminidase A (Tay-Sach’s disease). Hepatosplenomegaly Profile Leucocyte sphingomyelinase (Niemann-Pick A & B) Leucocyte β-glucosidase (Gaucher’s disease) Leucocyte acid esterase (Wolman’s disease & Cholesterol Ester Storage disease) Plasma chitotriosidase (Non specific screen for some lysosomal disorders such as Gaucher’s disease and Niemann Pick C– screening test only). Dysmorphic Profile (See http://www.metbio.net/metbioGuidelines.asp for guidelines) Plasma I-cell Screen (Mucolipidosis II & III) Plasma aspartylglucosaminidase (Aspartyglucosaminuria) Leucocyte arylsulphatase A (Multiple Sulphatase Deficiency) Plasma /Leucocyte β-glucuronidase (MPS VII) Leucocyte β-galactosidase (GM1 gangliosidosis & galactocerebrosidosis) Plasma/ Leucocyte α- & β-mannosidase (α- & β-mannosidosis) Plasma/ Leucocyte α-fucosidase (α-fucosidosis) Leucodystrophy Profile Leucocyte arylsulphatase A (Metachromatic leucodystrophy) Leucocyte β-galactocerebrosidase (Krabbe’s leucodystrophy). Battens Disease Profile Leucocyte palmitoyl protein thioesterase 1 (CLN1) Leucocyte tripeptidyl peptidase 1 (CLN2) Foetal/Neonatal Hydrops Profile (See http://www.metbio.net/metbioGuidelines.asp for guidelines). Leucocyte β-glucosidase (Gaucher’s Disease) Plasma/ Leucocyte β-glucuronidase (MPS VII) Leucocyte β-galactosidase (GM1 gangliosidosis & galactosialidosis), Leucocyte sphingomyelinase (Niemann-Pick A & B) Leucocyte acid esterase (Wolman’s disease & Cholesterol Ester Storage disease) Leucocyte arylsulphatase A (Metachromatic leucodystrophy) Plasma chitotriosidase (Non specific screen for some lysosomal disorders such as Gaucher’s disease and Niemann Pick C – screening test only). IMD laboratory handbook Document ID: DOC39 Version: 5 Page 12 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Non-Lysosomal Enzyme Assays Leucocytes Fructose 1,6 Bisphosphatase Steroid Sulphatase (aryl sulphatase C) VB (EDTA 10ml) VB (EDTA 5 ml), SB (Culture) Plasma Samples can be sent as whole blood or as separated plasma. Please send via round robin, courier or taxi. Do not send by first or second-class post. Biotinidase VB (Heparin 2ml) VB (Heparin, EDTA or clotted, 0.5ml) VP/VS 0.2ml Chitotriosidase Red Cells Samples should be sent as whole blood. Please send via round robin, courier or taxi. Do not send by first or second-class post. Glucose-6-Phosphate Dehydrogenase VB (1 ml preferably Heparin but EDTA is acceptable) Dihydropteridine Reductase (DHPR) 2x10mmBS Galactosaemia Screen VB (Heparin 0.5ml),2X10mm BS or red cells Tyrosinaemia screen (PBG synthase inhibition) VB (Heparin 0.5ml) 2x10mmBS or red cells. A blood transfusion within 6 weeks of sampling may invalidate results Cultured Fibroblasts Citrulline Incorporation (Citrullinaemia & Argininosuccinic Aciduria) SB (Culture) Cystine Incorporation (Cystinosis) SB (Culture) Ornithine Incorporation (Hyperornithinaemia with Gyrate Atrophy of the Retina & Hyperammonaemia with Hyperornithinaemia & SB (Culture) Homocitrullinuria) 14 Leucine CO2 Release (Maple Syrup Urine Disease) SB (Culture) Fatty Acid (myristate/oleate) Oxidation Flux Assays SB (Culture) 3 ( H Release Assays) 14 Butyrate CO2 Release (Short Chain Fatty Acid Oxidation Defects) SB (Culture) Isovaleric Acid Incorporation (Isovaleric Acidaemia & SB (Culture) Hydroxymethylglutaric Aciduria) Fumarylacetoacetate Lyase (Tyrosinaemia Type 1) SB (Culture) IMD laboratory handbook Document ID: DOC39 Version: 5 Page 13 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Tissues All tissue samples should be collected in liquid nitrogen or dry ice and stored at –800C before sending to our laboratory. All specimens should be sent frozen in dry ice (not in ice packs). Please contact the laboratory before sending. Fructose 1,6 Bisphosphatase (Fructose Bisphosphatase Deficiency) Duodenal Disaccharidases (Inherited Sucrase and Lactase Deficiency) Glycine Cleavage Enzyme (NonKetotic Hyperglycinaemia) Fumarylacetoacetate Lyase (Tyrosinaemia Type 1) IMD laboratory handbook Document ID: DOC39 Version: 5 Liver (Two Trucut Wedges) (at least 10 mg) Duodenal Tissue - at least 10mg Liver (Two Trucut Wedges) (at least 20 mg) Liver (Two Trucut Wedges) (at least 10 mg) Page 14 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS DNA ANALYSIS Sample requirement: - 3ml whole blood in EDTA sent at room temperature as whole blood or extracted DNA. The specimen can be sent by first class post. Analysis can also be performed on other material eg muscle, saliva, urine - please contact the laboratory concerning specimen requirements. Nuclear DNA Encoded Genes DISORDER Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD) Long Chain Acyl CoA Dehydrogenase Deficiency (LCHAD) Galactosaemia (Classical) McArdle Disease (Glycogen storage disease type V) Hereditary Fructose Intolerance (HFI) Myoadenylate Deaminase Deficiency (adenosine monophosphate deaminase 1) Carnitine Palmitoyl Transferase II Deficiency Pseudodeficiency State for Arylsulphatase A GENE MUTATION(S) METHOD Medium Chain Acyl CoA Dehydrogenase (ACADM) c.985A>G (p.Lys329Glu) PCR/RFLP c.1528G>C (p.Glu510Gln) PCR/RFLP c.563A>G (p.Gln188Arg) PCR/RFLP c.148C>T (p.Arg 50X) c.613G>A (p.Gly205Ser) PCR/RFLP Aldolase B (ALDOB) c.448G>C (p.Ala150Pro) PCR/RFLP Myoadenylate Deaminase (AMPD1) c.34C>T (p.Gln12X) Mitochondrial Trifunctional Protein Alpha Subunit (HADHA) Galactose-1-Phosphate Uridyl Transferase (GALT) Muscle Glycogen Phosphorylase (PYGM) Carnitine Palmitoyl Transferase 2 (CPT2) c.338C>T (p.Ser113Leu) PCR/RFLP Arylsulphatase A (ARSA) c.1524+95A>G PCR/RFLP Leigh Syndrome (Systemic Surfeit 1 (SURF1) Cytochrome Oxidase Deficiency) Fumarylacetoacetate hydrolase (FAH) Glycogen Storage Disease Type I Glucose-6-Phosphate Transporter (SLC37A4) Non-A Glycogen Storage Disease Type Glucose-6-phosphatase (G6PC) IA Tyrosinaemia Type I Menkes Disease Non-Ketotic Hyperglycinaemia (NKH) Glycine encephalopathy (GCE) Morquio Syndrome IVA ATP7A Glycine decarboxylase (GLDC) P Protein c.312_321delTCTGCCAGC PCR/ C311_312insAT (Common Fragment Analysis Mutation) Full gene sequencing DNA sequencing Common mutations and sequencing. Common mutations Targeted mutation analysis and sequencing. MLPA for deletions & Full gene sequencing and sequencing for point deletion/duplication analysis mutations Targeted mutation analysis Full gene sequencing and DNA sequencing and deletion/duplication analysis MLPA Amino methyl-transferase Full gene sequencing (AMT) Glycine cleavage analysis system T Protein (GCST) Galactosamine-6-sulphatase c.347G>T (p.Gly116Val) (GALNS) Cerebrotendinous xanthomatosis CYP27A1 (CTX) Juvenile neuronal ceroid CLN3 lipofuscinosis (JNCL) Batten disease type 3 IMD laboratory handbook Document ID: DOC39 Version: 5 PCR/RFLP DNA sequencing PCR/RFLP c.1184+1G>A PCR/RFLP 1.02kb deletion Deletion breakpoint PCR Page 15 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Mitochondrial DNA Encoded Mutations Mitochondrial DNA (TRNL1) m.3243A>G & m.3271T>C PCR/RFLP and ARMS analysis Mitochondrial DNA (TRNK) m.8344A>G PCR/RFLP Mitochondrial DNA (ATP6) m.8993 T>G/C PCR/RFLP Mitochondrial DNA (ATP6) m.9176T>C/G PCR/RFLP Mitochondrial DNA (ND5) m.13513G>A PCR/RFLP DEAF (Maternally Inherited Mitochondrial DNA (RNR1) Antibiotic Induced Deafness) Mitochondrial DNA (ND4) LHON (Leber’s Hereditary Mitochondrial DNA (ND1) Optic Neuropathy) Mitochondrial DNA (ND6) m.1555A>G PCR/RFLP m.11778G>A PCR/RFLP m.3460G>A PCR/RFLP m.14484T>C PCR/RFLP LDYT (Leber’s Hereditary Mitochondrial DNA (ND6) Optic Neuropathy with Dystonia & Leigh’s Syndrome) Mitochondrial DNA Kearns-Sayre Syndrome CPEO (Chronic Progressive External Ophthalmoplegia) Pearson Syndrome m.14459G>A PCR/RFLP MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes) MERRF (Myoclonic Epilepsy with Ragged Red Fibres) NARP (Neurogenic Muscle Weakness, Ataxia & Retinitis Pigmentosa) FBSN (Focal Bilateral Striatal Necrosis & Leigh Syndrome) LS (Leigh’s Syndrome) Rearrangements Long Range PCR Southern Blotting Group Tests of Mitochondrial DNA Mutations Leber’s Hereditary Optic Atrophy LHON m.11778G>A LHON m.3460G>A LHON m.14484T>C Mitochondrial DNA Screen MELAS m.3243A>G MERRF m.8344A>G NARP m.8993T>G or C Leigh’s Syndrome Profile FBSN m.9176C>T or G LS m.13513G>A LDYT m.14459G>A Long Range PCR for mtDNA Rearrangements The common mutation in the nuclear encoded SURF1 gene associated with systemic cytochrome oxidase deficiency. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 16 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS CELL CULTURE,TISSUE AND SAMPLE STORAGE Skin biopsies should be collected in a sterile manner (See Appendix) and transported unfrozen in tissue culture medium to guarantee to reach us within 24 hours of being taken. A guideline for sampling and storage is available. Skin biopsies will, in most cases, not be cultured immediately but will be frozen in cryopreservative medium and stored at –800C. If culture is required the biopsies can be thawed and in most cases cultured successfully up to at least 12 months after banking. The cultured fibroblasts grown will be cryopreserved in liquid nitrogen and stored unless disposal is specifically requested. Similarly all cultured lymphoblasts, cultured chorionic villus cells and cultured amniotic fluid cells will be cryopreserved and stored indefinitely. ?? Tissue specimens for eg liver, muscle, duodenum should be collected in small cryotubes (which can be provided) and ideally, frozen at the bedside in liquid nitrogen or dry ice. If this is not available the tubes should be put on water ice and immediately transferred to the coldest freezer available. Transport to our laboratory can then be arranged at a convenient date. Frozen tissue samples should be transported on dry ice. Where tissue specimens are stored a report is issued to this effect. Extracted DNA is stored indefinitely, unless disposal is specifically requested. GUIDELINES FOR INVESTIGATION The following guidelines are available as separate documents. Please contact the Duty Biochemist. Investigation of hypoglycaemia. Investigation of SUDI. Stroke and Metabolic Disorder. Hyperammonaemia. Cardiomyopathy. Developmental Delay. Seizures. Rhabdomyolysis There is a National Metabolic Biochemistry Network, which provides information about testing and guidelines for metabolic disorders. http://www.metbio.net/metbioGuidelines.asp TEACHING & EDUCATION We provide in house training for clinical scientists, biomedical scientists, chemical pathologists and other medical staff on the clinical and laboratory aspects of metabolic disorders. This is suitable for those studying for the MRCPath and other professional and academic examinations. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 17 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS If you wish one of our team to present a topic at your local Hospital please contact Mrs Mary Anne Preece. COSTS Within the West Midlands the laboratory IMD services are provided as a contract with the commissioners as part of the specialist services commissioning. Services not covered by this arrangement are charged for on a cost per test basis. A price list is available on request APPENDICES A. Guidelines for taking skin biopsies for tissue culture. B. Guidelines for emergency specimen collection (inherited metabolic disorder suspected) C. Investigation of Sudden Unexpected Death in Infancy. D. Laboratories to which tests are routinely referred. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 18 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS APPENDIX A: GUIDELINES ON TECHNIQUE OF SKIN BIOPSY FOR INHERITED METABOLIC DISORDERS When a sample of the skin is required for fibroblast culture for investigations for inherited metabolic disorders, a minor surgical procedure is undertaken in order to obtain a suitable biopsy sample.1 Skin biopsy taken via a punch device as detailed below is the preferred method; other methods include a shave biopsy or surgical excision. Under normal circumstances biopsies should not be taken without prior arrangement with the laboratory: Department of Newborn Screening and Biochemical Genetics, Birmingham Children's Hospital, Tel No. 0121 333 9942. NOTE THAT A SKIN BIOPSY IS OFTEN COLLECTED FOR HISTOLOGICAL ANALYSIS AND THAT THE SAMPLE HANDLING FOR THIS IS DIFFERENT. PLEASE CONTACT YOUR LOCAL HISTOPATHOLOGY DEPARTMENT FOR ADVICE. This procedure may be performed on the Ward, outpatients or in the operating theatre, by a trained Health care professional (any training should include the practical procedure, psychological aspects).2,3,4 A local anaesthetic is used when carrying out the procedure, rarely; oral sedation may also be required.5,6 An aseptic non-touch technique should be employed throughout the procedure.1,4,7,10 Consent must be obtained following BCH policy.8,9,11 Ensure the Skin Biopsy Consent form is signed and filed in the patient notes detailing consent to the procedure, analysis and storage of cells and asking whether patient/parents agree to subsequent storage of cells for quality control, comparison purposes and/or research. Information given should include the rationale for the biopsy, procedure and risks involved, side effects such as healing and scarring and a time line to expected results.4,12,13 The possibility of contamination or poor growth1 and repeat biopsy should be discussed where possible. Should a repeat biopsy be required referral to the play specialists may be appropriate. Equipment Plastic apron Sterile gloves Sterile dressing pack 25 Fg needle (orange) 23 Fg needle (blue) 2 ml syringe A labelled skin biopsy cryotube (Obtainable from IMD laboratory Ext 9942) 4mm Punch Device Lignocaine 1% Local anaesthetic and appropriate covering/dressing (Ametop gel or Emla cream) Normal saline sachet ChloraPrep Sepp (Chlorhexidine 2% in 70% alcohol) Steristrips Small Mepore dressing. Sterile scissors or scalpel blade Sample requirements A skin biopsy should be collected using a 4mm punch; smaller diameter punches may give insufficient sample for reliable culture. The inner sides of the forearm or posterior aspect just above the elbow are the preferred sites.1 IMD laboratory handbook Document ID: DOC39 Version: 5 Page 19 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Technique Apply local anaesthetic cream or gel to the biopsy site (following consultation with the family re allergies) and cover with appropriate dressing. Leave for a minimum of 30 minutes.1,5,6,13 Position the child, continue to maintain the dignity of the child whilst placing them in a comfortable position with the potential biopsy area exposed. Small children/infants can lie or sit on an adult’s lap. Ensure a young child has his/her favourite cuddly toy or comforter with him/her throughout.2,13 Prepare equipment and wash hands, put on apron and sterile gloves.4,7,10,14 Remove local anaesthetic cream and dressing and clean any residual cream from site.5 Sterilise the site with ChloraPrep Sepp, wait for the area to dry.7,11 Prepare local anaesthetic withdrawing from ampoule with blue needle, inject lignocane1% using orange needle. Placement of lignocaine should be intradermally with the majority subcutaneously such that an area 1.5 x1cm is affected.14 Wait 2-3 minutes. Clean area vigorously with normal saline using non woven swabs from dressing pack, and dry. Pull the skin tight, introduce the punch and rotate 360 degrees with the cutting edge carrying the punch down onto the tissue (the guard will prevent deep penetration).15 Withdraw the punch whilst applying pressure to site with a non-woven swab (found in dressing pack). Remove specimen using sterile forceps and scissors or scalpel. Without touching the biopsy, transfer immediately into the skin biopsy cryotube. Replace the screw cap. Apply pressure to wound with non woven swab until cessation of bleeding Apply Steristrips over wound.4 Cover with Mepore or another suitable dressing.4 Provide family with after care instructions, including analgesic dose should this be required.4,12,13 Dispose of equipment and waste per BCH policy.14 Send the sample immediately to the laboratory with a fully completed request form4,11 and the lower part of the Skin Biopsy Consent form. References 1. Olpin S. What are Biopsies, Cultures and Assays and what information do they provide? CLIMB update 2008;3:11-14 2. NMC. Professional code of conduct. April 2008. 3. GMC. Good Medical Practice. November 2008; 2(a). 4. BCH. Procedure for the collection, handling and transport of specimens. October 2005. 5. Clarke S, Radford M. Topical anaesthesia for venepuncture. Archives of Disease in Childhood.1986; 61: 1132-4. 6. BCH. Medicines policy. September 2008. 7. BCH. Guidance on the application of the aseptic technique and the aseptic non-touch technique when undertaking clinical procedures. March 2007. 8. BCH. Consent, Tissue and Bodily fluids policy. 2006. 9. BCH. Seeking and obtaining consent to treatment, examination and research with Children, Young People and those with “Parental Responsibility”. February 2006. 10. BCH. Policy for effective and appropriate hand hygiene. October 2006. 11. BCH. Procedure for the Collection handling and transport of specimens. October 2005. 12. GMC. Good Medical Practice. November 2008; 2(b). 13. BCH. Trust policy for the management of invasive/distressing procedures. February 2006. 14. BCH. Policy for the management of risks associated with needle stick injuries and mucous membrane exposures to blood and body fluids. January 2007 15. Great Ormond Street Hospital. Skin biopsy: punch method clinical guidelines. July 2007. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 20 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS APPENDIX B: GUIDELINES FOR EMERGENCY SPECIMEN COLLECTION (INHERITED METABOLIC DISORDER SUSPECTED) In life-threatening situations, where an inherited disorder is thought to be likely (either from family history, results of preliminary investigations or clinical presentation) appropriate specimens should be collected. At the earliest opportunity contact the metabolic laboratory duty biochemist (0121 333 9864) to discuss appropriate investigations. If possible, urine and blood specimens should be taken before death. Skin and tissue specimens, if not taken pre-mortem, should be taken as soon as possible after death. If any of the samples are taken after death it is extremely important to record accurately both the time of death and when the samples were taken. Appropriate storage as detailed below is essential. Local laboratories should make arrangements for suitable storage and transport of tissues to the specialist laboratory. URINE Urine, however little is extremely useful. Ideally 5-10ml should be stored. Collect into a bottle with no preservative and store deep frozen (-20oC or lower). If the specimen is contaminated with blood, centrifuge to remove cells before freezing the supernatant. BLOOD Collect 5-10ml in lithium heparin and 0.5ml in fluoride oxalate: separate the plasma as soon as possible and store the plasma deep frozen (-20oC). Store the packed red cells at +4oC (do not freeze). If DNA analysis is likely to be required, store a further 5-10ml of whole blood (EDTA) in a plastic tube at +4oC. SKIN (for fibroblast culture) Skin taken up to 24 hours after death is likely to be viable provided it is not infected. Take a skin biopsy and place it in tissue culture medium which is available from us or a suitable transport medium (obtainable from most Virology or Cytogenetics Departments). In emergency, sterile isotonic saline can be used, but do not use agar. The specimen should be stored at +4oC before despatch. Do not freeze. See Appendix A for further details.Transport to BCH by taxi or hospital transport to reach us within 24hours of collection. Sterility is of paramount importance when taking skin biopsy specimens, especially at necropsy. Tissue culture medium and a protocol are available on request. TISSUE SPECIMENS (Liver, heart muscle, skeletal muscle) Please ensure that these specimens are labelled with the type of tissue as well as the patient details. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 21 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Label the tubes prior to taking the specimens. Biopsies should only be taken if there is a strong clinical suspicion of a primary defect in one of these tissues. It is very important that blood and urine specimens are also taken and not just tissue specimens. Necropsy tissue specimens are suitable usually only for biochemical analysis if taken within two hours of death. Two or three needle biopsy specimens of tissue should be taken and placed in a small plastic tube. Immediately place a small piece of plastic film over the top of the specimen to prevent the biopsy drying out, cap the tube and snap freeze in liquid nitrogen (or solid CO2) and store in the coldest freezer available. If liquid nitrogen or solid CO2 are not available specimens must be stored immediately in the coldest freezer available. Please note that the collection procedures for tissue for biochemical analyses are not necessarily appropriate for histological tests and your local Histopathology Department should be contacted if specimens are required for histological analysis. Please contact the IMD service before sending samples and transport frozen specimens onsolid CO2 (dry ice) CEREBROSPINAL FLUID Sometimes a cerebrospinal fluid specimen may be useful. Collect a 1ml specimen. If blood stained, centrifuge and separate the supernatant. Store deep frozen. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 22 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS APPENDIX C: SUDDEN UNEXPLAINED DEATHS IN INFANCY (SUDI) SUDI Investigations should be carried out in all children less than 2 years of age who die suddenly and whose death is unexplained. This covers the investigation for:- Inherited Metabolic Disorders - Police Purposes (i.e. Forensic Laboratory and Radiology) in children who die - at home - en route/shortly after arrival at hospital - in hospital (Coroner’s case) SUMMARY OF SAMPLES REQUIRED Blood (heart stab) for; Blood culture (Pedplus/F) – Pedplus/F bottles are designed to take 0.5 – 5.0ml blood. The greater the sample volume, the more likely that bacteraemia can be detected. Lithium heparin specimen (at least 0.5ml) Guthrie card spots – These should ideally be prepared using fresh non-anticoagulated blood From the syringe. Place 4 drops of blood directly onto a labelled neonatal screening blood test card provided in the SUDS kit. Urine (bladder stab) Place into a sterile plastic universal container. If urine is unobtainable, but the nappy is wet, place the nappy in a plastic bag, seal and label. Naso-pharyngeal swab for virology The swab should be cut off, using scissors, into a bottle of viral transport medium. Skin for fibroblast culture. See the guidelines for skin biopsy protocol (Appendix A) At BCH, medium for skin biopsies are located in the refrigerator outside the resuscitation room in the emergency department. IMD laboratory handbook Document ID: DOC39 Version: 5 Page 23 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS APPENDIX D: LABORATORIES TO WHICH TESTS ARE ROUTINELY REFERRED Metabolites and enzymes Addenbrookes Hospital, Biochemical Genetics Unit Box 247 Hills Road Cambridge, CB2 2QQ Great Ormond Street Hospital Department of Chemical Pathology Great Ormond Street London WC1N 3JH University Hospital of Wales Department of Medical Biochemistry Heath Park Cardiff CF14 4XW Sheffield Childrens Hospital Department of Clinical Chemistry Western Bank Sheffield S10 2TH Guy's & St Thomas' Hospital, Purine Research Laboratory 4th Floor North Wing Westminster Bridge Road London SE1 7EH Neurometabolic Unit Box 105 National Hospital (UCLH Trust) Queen Square London WC1N 3BG Southmead Hospital Department of Clinical Biochemistry Blood Sciences Laboratories Southmead Hospital Bristol BS10 5NB University College London Hospitals Department of Clinical Biochemistry 60 Whitfield St London W1T 4EU IMD laboratory handbook Document ID: DOC39 Version: 5 Page 24 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Bristol Royal Infirmary Department of Clinical Biochemistry Bristol BS2 8HW Kings College Hospital Dept of Clinical Chemistry Denmark Hill London SE5 9RS Sahlgrenska University Hospital Clinical Chemistry Sahlgrenska Gothenburg Sweden Pole Biologie-Pathologie-Pharmacie Service de Virologie Bâtiment Jean Dausset - 6 étage, Hopital Cochin 27 rue du Faubourg Saint Jacques Paris France Academisch Medisch Centrum Laboratorium Genetische Metabole Ziekten Room FO-132A Meibergdreef 9 Amsterdam The Netherlands Potsdam MVZ GbR Institute fuer Medizinishe Diagnostik Berlin Nicolaistrasse 22 Berlin Germany Molecular tests West Midlands Regional Genetics Laboratory Birmingham Womens Hospital NHS Trust Metchley Park Road Edgbaston Birmingham B15 2TG Sheffield Diagnostic Genetics Service (Molecular) Sheffield Diagnostics Genetics Service Sheffield Children's NHS Foundation Trust Western Bank Sheffield S10 2TH IMD laboratory handbook Document ID: DOC39 Version: 5 Page 25 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece BIRMINGHAM CHILDREN’S HOSPITAL NHS FOUNDATION TRUST PAEDIATRIC LABORATORY MEDICINE DEPARTMENT OF NEWBORN SCREENING AND BIOCHEMICAL GENETICS Oxford RGC Oxford Radcliffe Hospitals NHS Trust The Churchill Old Road, Headington Oxford OX3 7LJ NEWCASTLE MITOCHONDRIAL NSCAG DIAGNOSTIC LABORATORY Mitochondrial Research Group 4th Floor, The Medical School Newcastle University, Framlington Place Newcastle upon Tyne, NE2 4HH. West of Scotland Regional Molecular Genetics Laboratory (Glasgow) West of Scotland Regional Molecular Genetics Laboratory Duncan Guthrie Institue of Medical Genetics, Yorkhill Hospital Dalnair Road Glasgow G3 8SJ London North East Thames RGC (Great Ormond Street Hospital) NE Thames Regional Molecular Genetics Laboratory, Great Ormond Street Hospital NHS Trust Level 6 York House 37 Queen Square London WC1N 3BH DNA Laboratory, GSTS Pathology, Guys Hospital Genetics Centre Guys Hospital London SE1 9RT Department of Clinical Genetics - VU University Medical Center (Amsterdam) Department of Clinical Genetics - VU University Medical Center (Amsterdam) Laboratorium voor DNA en Eiwitdiagnostiek De Boelelaan 1117 NL-1081 HV Amsterdam NETHERLANDS Yorkshire RGC (Leeds) Yorkshire Regional DNA Laboratory Ashley Wing St James's University Hospital Leeds LS9 7TF IMD laboratory handbook Document ID: DOC39 Version: 5 Page 26 of 26 Date of issue: July 2013 Final Authoriser: Mary Anne Preece
© Copyright 2024