Guthrie test

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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.

Introduction

Dr Robert Guthrie
Dr Robert Guthrie
Guthrie card
A neonatal blood screening test developed by Dr Robert Guthrie (1916-95) at University of Buffalo. By 1963 the test had become a routine neonatal test for phenylketonuria[1]


The "Heel Prick" test.


The Guthrie test or "Heel Prick" test is routinely carried out on neonatal (newborn) blood for a variety of known genetic disorders. The clinical term "phlebotomy" describes the act of drawing or removing blood from the circulatory system through an incision or puncture to obtain a sample for analysis and diagnosis.

Different countries have different policies on:

  1. disorders included in the test
  2. archiving of this material
  3. deidentified availability for genetic research purposes.


An ultrasound study[2] has identified the shortest depth of perichondrium was in the centre of the heel and ranged from 3 to 8 mm. In 78 of the 80 infants in the study (GA24 to 42 weeks), the distance was 4 mm or more. Showing that the standard automated lancets for preterm use (puncture to a depth of 2.4 mm) may be safely used anywhere over the plantar surface of the heel avoiding the posterior aspect of the heel. A more recent study[3] identified the whole heel plantar surface is safe for obtaining blood in term and preterm infants of more than GA 33 weeks. A small amount of sucrose (0.012–0.12 g) can be given as an analgesic for newborns undergoing venepuncture or capillary heel-pricks.[4]



Blood is collected using a heelprick and spotted onto a test sheet to dry for later testing. Different countries and medical services have different policies on not only what will be tested for but also how long the test card will be kept following analysis. Check your local service for specific information.


Diagnosis Links: Prenatal Diagnosis | Pregnancy Test | Amniocentesis | Chorionic villus sampling | Ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

Some Recent Findings

UK Neonatal blood spot test (August 2013)
  • Review - Aminoacidopathies - Prevalence, Etiology, Screening, and Treatment Options[5]
  • Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes[6] "Many inborn errors of metabolism (IEMs) may present as sudden infant death (SID). Nowadays, increasing numbers of patients with IEMs are identified pre-symptomatically by population neonatal bloodspot screening (NBS) programmes. However, some patients escape early detection because their symptoms and signs start before NBS test results become available, they even die even before the sample for NBS has been drawn or because there are IEMs which are not included in the NBS programmes. This was a comprehensive systematic literature review to identify all IEMs associated with SID, including their treatability and detectability by NBS technologies. Reye syndrome (RS) was included in the search strategy because this condition can be considered a possible pre-stage of SID in a continuum of aggravating symptoms. RESULTS: 43 IEMs were identified that were associated with SID and/or RS. Of these, (1) 26 can already present during the neonatal period, (2) treatment is available for at least 32, and (3) 26 can currently be identified by the analysis of acylcarnitines and amino acids in dried bloodspots (DBS). We advocate an extensive analysis of amino acids and acylcarnitines in blood/plasma/DBS and urine for all children who died suddenly and/or unexpectedly, including neonates in whom blood had not yet been drawn for the routine NBS test. The application of combined metabolite screening and DNA-sequencing techniques would facilitate fast identification and maximal diagnostic yield."
  • UK National Screening Committee - Newborn babies will be tested for four more disorders[7] "The test is already used to screen for phenylketonuria, hypothyroidism, sickle cell disease, cystic fibrosis, and medium chain acyl-CoA dehydrogenase deficiency. To these five conditions four more will now be added: homocystinuria, maple syrup urine disease, glutaric aciduria type 1, and isovaleric acidaemia."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: neonatal blood test

George Kassim Chilinda, Luis Aaron Gadama, William Stones Point-of-care umbilical arterial lactate and newborn outcomes in a low resource setting: cohort study. BMC Res Notes: 2018, 11(1);477 PubMed 30012214

Mutaz Dana, Eitan Fibach Elimination of ABO Blood Group Incompatible Fetal Red Blood Cells in the Maternal Circulation: Relevance to the Diagnosis of Fetal-Maternal Hemorrhage. Neonatology: 2018, 114(4);303-306 PubMed 30011398

L Song, Y Li, G X Peng, L Zhang, L P Jing, K Zhou, Y Li, L Ye, J P Li, H H Fan, X Zhao, W R Yang, Y Yang, Y P Zhao, Y Z Xiong, Z J Wu, F K Zhang [The clinical and laboratory characteristics of congenital pyruvate kinase deficiency]. Zhonghua Nei Ke Za Zhi: 2018, 57(7);511-513 PubMed 29996270

Adeeb Khalifeh, Rebecca Eckler, Laura Felder, Gabriele Saccone, Claudia Caissutti, Vincenzo Berghella One-step versus two-step diagnostic testing for gestational diabetes: a randomized controlled trial. J. Matern. Fetal. Neonatal. Med.: 2018;1-171 PubMed 29985079

Tianyan Chen, Jing Wang, Hongtao Qiu, Qiang Yu, Taotao Yan, Caijing Qi, Furong Cao, Zhen Tian, Dandan Guo, Naijuan Yao, Yuan Yang, Yingli He, Yingren Zhao, Jinfeng Liu Different interventional criteria for chronic hepatitis B pregnant women with HBeAg(+) or HBeAg(-): Epidemiological data from Shaanxi, China. Medicine (Baltimore): 2018, 97(27);e11406 PubMed 29979437


Search term: Guthrie test

Susan J de Jersey, Jeanette Tyler, Taylor Guthrie, Karen New Supporting healthy weight gain and management in pregnancy: Does a mandatory training education session improve knowledge and confidence of midwives? Midwifery: 2018, 65;1-7 PubMed 30005316

Amy Y Liu, Stephen C De Rosa, Brandon L Guthrie, Robert Y Choi, Rose Kerubo-Bosire, Barbra A Richardson, James Kiarie, Carey Farquhar, Barbara Lohman-Payne High background in ELISpot assays is associated with elevated levels of immune activation in HIV-1-seronegative individuals in Nairobi. Immun Inflamm Dis: 2018; PubMed 29974672

Matthew Dunster-Jones, Michelle Steicke, James Mackie, Rachel Guthrie, Tam Nguyen Din, Fahima Ahmady, Jonathan Golledge, Yutang Wang The concentration of ethanol affects its penetration rate in bovine cardiac and hepatic tissues. Folia Histochem. Cytobiol.: 2018; PubMed 29873057

Cindy Mann, Alison Shaw, Lesley Wye, Chris Salisbury, Bruce Guthrie A computer template to enhance patient-centredness in multimorbidity reviews: a qualitative evaluation in primary care. Br J Gen Pract: 2018; PubMed 29784866

Ni Zhao, Xiang Zhan, Katherine A Guthrie, Caroline M Mitchell, Joseph Larson Generalized Hotelling's test for paired compositional data with application to human microbiome studies. Genet. Epidemiol.: 2018; PubMed 29737047

Older papers  
  • The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States[8] "We aimed to measure separately the contributions of heat and humidity to changes in levels of 34 markers of inborn disorders in dried-blood-spot (DBS) samples. We stored paired sets of DBSs at 37°C for predetermined intervals in low-humidity and high-humidity environments. Marker levels of all samples in each complete sample set were measured in a single analytic run. During the 30 ± 5 day studies, galactose-1-phosphate uridyltransferase and biotinidase lost almost 65% of initial activities in low-humidity storage; most of the degradation in 27 other markers was attributable to adverse effects of high-humidity storage; seven markers in DBSs stored at high humidity lost more than 90% of initial levels by the end of the study and 4 of the 7 lost more than 50% of initial levels within the first week of storage."
  • Newborn hearing screening and genetic testing in 8974 Brazilian neonates.[9] "We have found 17 individuals who failed in transient otoacoustic emissions (TOAE). Among them, we detected 4 homozygous newborns for 35delG mutation and 3 individuals with A827G mutation in the MTRNR1 mitochondrial gene."
  • Whole genome microarray analysis, from neonatal blood cards.[10] "Neonatal blood, obtained from a heel stick and stored dry on paper cards, has been the standard for birth defects screening for 50 years. Such dried blood samples are used, primarily, for analysis of small-molecule analytes. More recently, the DNA complement of such dried blood cards has been used for targeted genetic testing, such as for single nucleotide polymorphism in cystic fibrosis. Expansion of such testing to include polygenic traits, and perhaps whole genome scanning, has been discussed as a formal possibility. However, until now the amount of DNA that might be obtained from such dried blood cards has been limiting, due to inefficient DNA recovery technology. ...Together, these data suggest that DNA obtained from less than 10% of a standard neonatal blood specimen, stored dry for several years on a Guthrie card, can support a program of genome-wide neonatal genetic testing."

Routine Screened Disorders

This list may differ between countries.

  • Phenylketonuria (PKU)
  • Biotinidase Deficiency (OMIM)
  • Congenital Adrenal Hyperplasia (CAH) (OMIM)
  • Congenital Hypothyroidism (CH)
  • Congenital Toxoplasmosis
  • Cystic Fibrosis (CF) (OMIM)
  • Galactosemia (GAL) (OMIM)
  • Homocystinuria (OMIM)
  • Maple Syrup Urine Disease (MSUD) (OMIM)
  • Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) (OMIM)
  • Toxoplasma gondii IgM antibodies[11]

Phenylketonuria

Incidence is about 1 in 10,000 live births (about 10 babies per year). PKU causes high blood levels of phenylalanine and severe intellectual disability. A diet low in phenylalanine, started in the first two to three weeks results in normal development.


PubMed Search - Phenylketonuria

Galactosaemia

Galactosaemia incidence is about 1 in 40,000 births, about 1-3 cases per year. See a recent disease review[12] and a Cochrane Database review.[13] Babies cannot process galactose, a component of lactose. Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first week can be life saving.


Links: milk
PubMed Search - Galactosaemia

Australia

NSW Newborn Screening Programme

NSW Newborn Screening Programme

Each year test more than 90,000 babies and detects about 90 who need urgent assessment and treatment. In NSW and Victoria, the bloodspot cards are currently stored indefinitely.

  • Phenylketonuria (PKU) - 1 in 10,000 live births (about 10 babies per year). PKU causes high blood levels of phenylalanine and severe intellectual disability. A diet low in phenylalanine, started in the first two to three weeks results in normal development.
  • Primary congenital hypothyroidism - 1 in 3,500 live births (about 26 babies per year). It is caused by the absence or abnormal formation or function of the thyroid gland. This causes growth and intellectual disability if not treated. Medication with thyroid hormone started early, results in normal growth and development.
  • Cystic Fibrosis (CF) - 1 in 2,500 live births (about 34 babies per year). Without treatment babies develop chest infections and often have very serious failure to thrive. Early institution of treatment greatly improves the health of babies with CF. Newborn bloodspot screening detects about 95% of babies with CF but also detects a few babies who may only be healthy carriers. For these babies a sweat test at about six weeks of age determines whether the baby has CF or is a healthy carrier.
  • Galactosaemia - 1 in 40,000 births (about 1-3 cases per year). Babies cannot process galactose, a component of lactose. Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first week is life saving.
  • Rarer metabolic disorders - Some fatty acid, organic acid and other amino acid defects can now be detected using Tandem Mass Spectrometry. These much rarer metabolic disorders affect about 15 – 18 babies per year. Early detection is important as diet and medications can treat most of these disorders. Without appropriate management they can cause severe disability or death.

Potential uses and access of stored bloodspots

  • Identified cards may be used for family benefit or research and only with separate consent obtained before testing.
  • Non-identifiable cards (identifiers permanently removed) may be used for research approved by a Health Research Ethics Committee – consent is not required.
  • Parents have a right to access their child’s information. Other access requires parental consent except where there is a court order, to date this has not occurred.


Genetics services in NSW - coordinated by the NSW Genetics Service Advisory Committee, which is supported by the Statewide Services Development Branch of the Strategic Development Division, NSW Department of Health. (Information from NSW Health - Newborn Bloodspot Screening Policy 13-Nov-2006)


Links: NSW Genetics Health

USA

State laws mandate that blood be drawn from all newborn infants to screen for health-threatening conditions.

References

  1. GUTHRIE R & SUSI A. (1963). A SIMPLE PHENYLALANINE METHOD FOR DETECTING PHENYLKETONURIA IN LARGE POPULATIONS OF NEWBORN INFANTS. Pediatrics , 32, 338-43. PMID: 14063511
  2. Jain A & Rutter N. (1999). Ultrasound study of heel to calcaneum depth in neonates. Arch. Dis. Child. Fetal Neonatal Ed. , 80, F243-5. PMID: 10212093
  3. Arena J, Emparanza JI, Nogués A & Burls A. (2005). Skin to calcaneus distance in the neonate. Arch. Dis. Child. Fetal Neonatal Ed. , 90, F328-f331. PMID: 15871987 DOI.
  4. Stevens B, Yamada J & Ohlsson A. (2004). Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev , , CD001069. PMID: 15266438 DOI.
  5. Wasim M, Awan FR, Khan HN, Tawab A, Iqbal M & Ayesha H. (2018). Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options. Biochem. Genet. , 56, 7-21. PMID: 29094226 DOI.
  6. van Rijt WJ, Koolhaas GD, Bekhof J, Heiner Fokkema MR, de Koning TJ, Visser G, Schielen PC, van Spronsen FJ & Derks TG. (2016). Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes. Neonatology , 109, 297-302. PMID: 26907928 DOI.
  7. Hawkes N. (2014). Newborn babies will be tested for four more disorders, committee decides. BMJ , 348, g3267. PMID: 25134132
  8. Adam BW, Hall EM, Sternberg M, Lim TH, Flores SR, O'Brien S, Simms D, Li LX, De Jesus VR & Hannon WH. (2011). The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States. Clin. Biochem. , 44, 1445-50. PMID: 21963384 DOI.
  9. Nivoloni Kde A, da Silva-Costa SM, Pomílio MC, Pereira T, Lopes Kde C, de Moraes VC, Alexandrino F, de Oliveira CA & Sartorato EL. (2010). Newborn hearing screening and genetic testing in 8974 Brazilian neonates. Int. J. Pediatr. Otorhinolaryngol. , 74, 926-9. PMID: 20538352 DOI.
  10. Hardin J, Finnell RH, Wong D, Hogan ME, Horovitz J, Shu J & Shaw GM. (2009). Whole genome microarray analysis, from neonatal blood cards. BMC Genet. , 10, 38. PMID: 19624846 DOI.
  11. The national neonatal screening programme for congenital toxoplasmosis in Denmark: results from the initial four years, 1999-2002. Schmidt DR, Hogh B, Andersen O, Fuchs J, Fledelius H, Petersen E. Arch Dis Child. 2006 Aug;91(8):661-5. PMID: 16861484]
  12. Demirbas D, Coelho AI, Rubio-Gozalbo ME & Berry GT. (2018). Hereditary Galactosemia. Metab. Clin. Exp. , , . PMID: 29409891 DOI.
  13. Lak R, Yazdizadeh B, Davari M, Nouhi M & Kelishadi R. (2017). Newborn screening for galactosaemia. Cochrane Database Syst Rev , 12, CD012272. PMID: 29274129 DOI.


Reviews

van der Spek J, Groenwold RH, van der Burg M & van Montfrans JM. (2015). TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review. J. Clin. Immunol. , 35, 416-30. PMID: 25893636 DOI.

Articles

Adam BW, Hall EM, Sternberg M, Lim TH, Flores SR, O'Brien S, Simms D, Li LX, De Jesus VR & Hannon WH. (2011). The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States. Clin. Biochem. , 44, 1445-50. PMID: 21963384 DOI.

Streetly A, Latinovic R, Hall K & Henthorn J. (2009). Implementation of universal newborn bloodspot screening for sickle cell disease and other clinically significant haemoglobinopathies in England: screening results for 2005-7. J. Clin. Pathol. , 62, 26-30. PMID: 19103854 DOI.

Whiteman PD, Clayton BE, Ersser RS, Lilly P & Seakins JW. (1979). Changing incidence of neonatal hypermethioninaemia: implications for the detection of homocystinuria. Arch. Dis. Child. , 54, 593-8. PMID: 507913

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Cite this page: Hill, M.A. (2018, July 18) Embryology Guthrie test. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Guthrie_test

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