Talk:Guthrie test

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Cite this page: Hill, M.A. (2021, December 2) Embryology Guthrie test. Retrieved from


van Vliet K, van Ginkel WG, van Dam E, de Blaauw P, Koehorst M, Kingma HA, van Spronsen FJ & Heiner-Fokkema MR. (2020). Dried blood spot versus venous blood sampling for phenylalanine and tyrosine. Orphanet J Rare Dis , 15, 82. PMID: 32245393 DOI.

Dried blood spot versus venous blood sampling for phenylalanine and tyrosine

Background: This study investigated the agreement between various dried blood spot (DBS) and venous blood sample measurements of phenylalanine and tyrosine concentrations in Phenylketonuria (PKU) and Tyrosinemia type 1 (TT1) patients.

Study design: Phenylalanine and tyrosine concentrations were studied in 45 PKU/TT1 patients in plasma from venous blood in lithium heparin (LH) and EDTA tubes; venous blood from LH and EDTA tubes on a DBS card; venous blood directly on a DBS card; and capillary blood on a DBS card. Plasma was analyzed with an amino acid analyzer and DBS were analyzed with liquid chromatography-mass spectrometry. Agreement between different methods was assessed using Passing and Bablok fit and Bland Altman analyses.

Results: In general, phenylalanine concentrations in LH plasma were comparable to capillary DBS, whereas tyrosine concentrations were slightly higher in LH plasma (constant bias of 6.4 μmol/L). However, in the low phenylalanine range, most samples had higher phenylalanine concentrations in DBS compared to LH plasma. Remarkably, phenylalanine and tyrosine in EDTA plasma were higher compared to all other samples (slopes ranging from 7 to 12%). No differences were observed when comparing capillary DBS to other DBS.

Conclusions: Overall agreement between plasma and DBS is good. However, bias is specimen- (LH vs EDTA), and possibly concentration- (low phenylalanine) dependent. Because of the overall good agreement, we recommend the use of a DBS-plasma correction factor for DBS measurement. Each laboratory should determine their own factor dependent on filter card type, extraction and calibration protocols taking the LH plasma values as gold standard.

Pellegrinelli L, Alberti L, Pariani E, Barbi M & Binda S. (2020). Diagnosing congenital Cytomegalovirus infection: don't get rid of dried blood spots. BMC Infect. Dis. , 20, 217. PMID: 32164599 DOI.

Diagnosing congenital Cytomegalovirus infection: don't get rid of dried blood spots

Background: Congenital Cytomegalovirus (cCMV) is a serious global public health issue that can cause irreversible fetal and neonatal congenital defects in symptomatic or asymptomatic newborns at birth. In absence of universal cCMV screening, the retrospective diagnosis of cCMV infection in children is only possible by examining Dried Blood Spot (DBS) samples routinely collected at birth and stored for different time spans depending on the newborn screening regulations in force in different countries. In this article, we summarize the arguments in favor of long-term DBS sample storage for detecting cCMV infection.

Main text: CMV infection is the most common cause of congenital infection resulting in severe defects and anomalies that can be apparent at birth or develop in early childhood. Sensorineural hearing loss is the most frequent consequence of cCMV infection and may have a late onset and progress in the first years of life. The virological diagnosis of cCMV is essential for clinical research and public health practices. In fact, in order to assess the natural history of CMV infection and distinguish between congenital or acquired infection, children should be diagnosed early by analyzing biological samples collected in the first weeks of life (3 weeks by using viral culture and 2 weeks by molecular assays), which, unfortunately, are not always available for asymptomatic or mildly symptomatic children. It now seems possible to overcome this problem since the CMV-DNA present in the blood of congenitally infected newborns can be easily retrieved from the DBS samples on the Guthrie cards routinely collected and stored within 3 days from birth in the neonatal screening program for genetic and congenital diseases. Early collection and long-term storage are inexpensive methods for long-term bio-banking and are the key points of DBS testing for the detection of cCMV.

Conclusion: DBS sampling is a reliable and inexpensive method for long-term bio-banking, which enables to diagnose known infectious diseases - including cCMV - as well as diseases not jet recognized, therefore their storage sites and long-term storage conditions and durations should be the subject of political decision-making.


5C56 Lysosomal diseases

5C56.0 Sphingolipidosis - 5C56.00 Gangliosidosis | 5C56.01 Fabry disease | 5C56.02 Metachromatic leukodystrophy

Coded Elsewhere Krabbe disease (8A44.4) Niemann-Pick disease type C (5C56.0Y) Niemann-Pick disease type A (5C56.0Y) Niemann-Pick disease type B (5C56.0Y)

5C56.1 Neuronal ceroid lipofuscinosis - Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited progressive degenerative brain diseases characterized clinically by a decline of mental and other capacities, epilepsy, and vision loss through retinal degeneration, and histopathologically by intracellular accumulation of an autofluorescent material, ceroid lipofuscin, in the neuronal cells in the brain and in the retina.

5C56.2 Glycoproteinosis - These are lysosomal storage diseases affecting glycoproteins, resulting from defects in lysosomal function. The term is sometimes reserved for conditions involving degradation of glycoproteins.

5C56.3 Mucopolysaccharidosis - Disorders of glycosaminoglycan metabolism

5C56.4 Disorders of sialic acid metabolism - This refers to any disorders of the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone.

Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal

Orphanet J Rare Dis. 2019 Feb 8;14(1):33. doi: 10.1186/s13023-019-1016-6.

Yadak R1, Breur M2, Bugiani M3. Author information Abstract BACKGROUND: MNGIE is a rare and fatal disease in which absence of the enzyme thymidine phosphorylase induces systemic accumulation of thymidine and deoxyuridine and secondary mitochondrial DNA alterations. Gastrointestinal (GI) symptoms are frequently reported in MNGIE patients, however, they are not resolved with the current treatment interventions. Recently, our understanding of the GI pathology has increased, which rationalizes the pursuit of more targeted therapeutic strategies. In particular, interstitial cells of Cajal (ICC) play key roles in GI physiology and are involved in the pathogenesis of the GI dysmotility. However, understanding of the triggers of ICC deficits in MNGIE is lacking. Herein, we review the current knowledge about the pathology of GI dysmotility in MNGIE, discuss potential mechanisms in relation to ICC loss/dysfunction, remark on the limited contribution of the current treatments, and propose intervention strategies to overcome ICC deficits. Finally, we address the advances and new research avenues offered by organoids and tissue engineering technologies, and propose schemes to implement to further our understanding of the GI pathology and utility in regenerative and personalized medicine in MNGIE. CONCLUSION: Interstitial cells of Cajal play key roles in the physiology of the gastrointestinal motility. Evaluation of their status in the GI dysmotility related to MNGIE would be valuable for diagnosis of MNGIE. Understanding the underlying pathological and molecular mechanisms affecting ICC is an asset for the development of targeted prevention and treatment strategies for the GI dysmotility related to MNGIE. KEYWORDS: CIPO; Chronic intestinal pseudo-obstruction; HSCT; ICC; Interstitial cells of Cajal; Intestinal organoids; MNGIE; Mitochondrial neurogastrointestinal encephalomyopathy PMID: 30736844 PMCID: PMC6368792 DOI: 10.1186/s13023-019-1016-6


Economic impact of screening for X-linked Adrenoleukodystrophy within a newborn blood spot screening programme

Orphanet J Rare Dis. 2018 Oct 11;13(1):179. doi: 10.1186/s13023-018-0921-4.

Bessey A1, Chilcott JB2, Leaviss J2, Sutton A2.


BACKGROUND: A decision tree model was built to estimate the economic impact of introducing screening for X-linked adrenoleukodystrophy (X-ALD) into an existing tandem mass spectrometry based newborn screening programme. The model was based upon the UK National Health Service (NHS) Newborn Blood Spot Screening Programme and a public service perspective was used with a lifetime horizon. The model structure and parameterisation were based upon literature reviews and expert clinical judgment. Outcomes included health, social care and education costs and quality adjusted life years (QALYs). The model assessed screening of boys only and evaluated the impact of improved outcomes from hematopoietic stem cell transplantation in patients with cerebral childhood X-ALD (CCALD). Threshold analyses were used to examine the potential impact of utility decrements for non-CCALD patients identified by screening. RESULTS: It is estimated that screening 780,000 newborns annually will identify 18 (95%CI 12, 27) boys with X-ALD, of whom 10 (95% CI 6, 15) will develop CCALD. It is estimated that screening may detect 7 (95% CI 3, 12) children with other peroxisomal disorders who may also have arisen symptomatically. If results for girls are returned an additional 17 (95% CI 12, 25) cases of X-ALD will be identified. The programme is estimated to cost an additional £402,000 (95% CI £399-407,000) with savings in lifetime health, social care and education costs leading to an overall discounted cost saving of £3.04 (95% CI £5.69, £1.19) million per year. Patients with CCALD are estimated to gain 8.5 discounted QALYs each giving an overall programme benefit of 82 (95% CI 43, 139) QALYs. CONCLUSION: Including screening of boys for X-ALD into an existing tandem mass spectrometry based newborn screening programme is projected to reduce lifetime costs and improve outcomes for those with CCALD. The potential disbenefit to those identified with non-CCALD conditions would need to be substantial in order to outweigh the benefit to those with CCALD. Further evidence is required on the potential QALY impact of early diagnosis both for non-CCALD X-ALD and other peroxisomal disorders. The favourable economic results are driven by estimated reductions in the social care and education costs. KEYWORDS: Adrenoleukodystrophy; Cost-benefit analysis; Cost-effectiveness analysis; Decision trees; Economic analysis; Hematopoietic stem cell transplantation; Neonatal screening; Newborn screening PMID: 30309370 PMCID: PMC6182830 DOI: 10.1186/s13023-018-0921-4


Inborn Errors of Metabolism That Cause Sudden Infant Death: A Systematic Review with Implications for Population Neonatal Screening Programmes

Neonatology. 2016 Feb 24;109(4):297-302. [Epub ahead of print]

van Rijt WJ1, Koolhaas GD, Bekhof J, Heiner Fokkema MR, de Koning TJ, Visser G, Schielen PC, van Spronsen FJ, Derks TG.


BACKGROUND: 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. OBJECTIVES AND METHODS: 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). CONCLUSION: 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. This is important information for clinicians who need to maintain clinical awareness and decision-makers to improve population NBS programmes. © 2016 S. Karger AG, Basel.

PMID 26907928


TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review

J Clin Immunol. 2015 Apr 17. [Epub ahead of print]

van der Spek J1, Groenwold RH, van der Burg M, van Montfrans JM. Author information Abstract BACKGROUND: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) in neonatal dried blood spots (DBS) enables early diagnosis of severe combined immunodeficiency disease (SCID). In recent years, different screening algorithms for TREC based SCID screening were reported. PURPOSE: To systematically review the diagnostic performance of published algorithms for TREC based NBS for SCID. METHODS: PubMed, EMBASE and the Cochrane Library were systematically searched for case series and prospective cohort studies describing TREC based NBS for SCID. We extracted TREC content and cut-off values, number of retests, repeat DBS and referrals, and type and number of typical SCID and other T cell lymphopenia (TCL) cases. We calculated positive predictive value (PPV), test sensitivity and SCID incidence. RESULTS: Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. In case series, the sensitivity for typical SCID was 100 %. In the prospective cohort studies, SCID incidence was ~1.7:100,000, re-test rate was 0.20-3.26 %, repeat DBS rate 0.0-0.41 % and referral rate 0.01-1.35 %. PPV within the five largest cohorts was 0.8-11.2 % for SCID and 18.3-81.0 % for TCL. Individual TREC contents in all SCID patients was <25 TRECs/μl (except in those evaluated with the New York State assay). CONCLUSIONS: The sensitivity of TREC based NBS for typical SCID was 100 %. The TREC cut-off score determines the percentage of non-SCID TCL cases detected in newborn screening for TCL. Adapting the screening algorithm for pre-term/ill infants reduces the amount of false positive test results.

PMID 25893636


Newborn babies will be tested for four more disorders, committee decides

BMJ 2014; 348 doi: (Published 13 May 2014)

Cite this as: BMJ 2014;348:g3267

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.


To reduce the pain of heel prick in the newborn: comparison of six types of lancets

Pediatr Med Chir. 2012 Jul-Aug;34(4):182-5.

[Article in Italian]

Ballardini G1, Spruzzola A, Boneschi L, Visentin R, Boscardini L, Barbaglia M, Guala LA. Author information Abstract Heel prick is an usual method performed to get a blood sample for newborn screening. Its wide use justifies the effort in reducing the pain as much as possible and some simple steps, including the use of spring heelsticks, are recommended by national and international guide-lines. But not all the heelsticks cause the same pain and allow to get enough blood for the screening. The aim of this work was to test six automatic heelstick devices with regard to the pain in heel prick measured with NIPS scale and, at the same time, to value their effectiveness in getting a blood sample suitable for filter paper for newborn screening. The following devices were assessed: Amnes Minilet Lancets, Wuxi Xinda Ltd, Exxe Safe Blade, Lifescan Stik Johnson & Johnson, One Touch Ultra Soft, Accu-Chek Safe T Pro Plus. The device Exxe Safe Blade statistically differs from all others: it is the least painful and it doesn't need any prick repetition.

PMID 23173410

Chromosome 22q11.2 duplication is rare in a population-based cohort of Danish children with cardiovascular malformations

Am J Med Genet A. 2012 Mar;158A(3):509-13. doi: 10.1002/ajmg.a.34441. Epub 2012 Feb 2.

Agergaard P, Olesen C, Østergaard JR, Christiansen M, Sørensen KM. Source Department of Pediatrics, Viborg Hospital, Viborg, Denmark.


The prevalence of the 22q11.2 duplication is unknown in children with cardiovascular malformations (CVMs). As most individuals with the duplication are detected in the search for other conditions, especially the 22q11.2 deletion, CVMs associated with the duplication are subject to referral bias. We circumvented this bias by investigating the prevalence of the 22q11.2 duplication in a population-based cohort of children with CVMs. The study population was defined as children born in 2000-2008, who were registered in the Danish National Patient Registry with a diagnosis of CVM from one of the two national university departments of pediatric cardiology. Sensitive multiplex ligation-dependent probe amplification was performed on dried blood spot samples from each individual's neonatal screening test. The study population consisted of 2,952 children with CVMs, 2,424 of whom were eligible for genetic testing; 13 individuals (0.5% [0.3-0.9%]) carried the duplication. Nine individuals (69%) had not previously been tested for a copy number variation on chromosome 22q11.2 in the clinical setting for children with CVMs. We conclude that 22q11.2 duplication is rare in children with CVMs, and is primarily found in malformations that are also associated with the 22q11.2 deletion. Copyright © 2012 Wiley Periodicals, Inc.

PMID 22302736

Evaluation of current guthrie TSH cut-off point in Iran congenital hypothyroidism screening program: a cost-effectiveness analysis

Arch Iran Med. 2012 Mar;15(3):136-41.

Shamshiri AR, Yarahmadi S, Forouzanfar MH, Haghdoost AA, Hamzehloo G, Holakouie Naieni K. Source Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Abstract BACKGROUND: The threshold of thyroid-stimulating hormone (TSH) in current screening for congenital hypothyroidism (CH) from the heel prick test is 5 mU/l. This study uses cost-effective analysis to evaluate increasing the threshold to minimize false-positive results and recall rates. METHODS: Cost of screening, diagnosis and treatment, education, and care of mentally retarded patients were gathered from the Ministry of Health State Welfare Organization and Department of Education in Tehran. Screening data were obtained from 34,007 neonates in the Central Health Laboratory of Tehran University of Medical Sciences in 2009. Sensitivity analysis and calculation of confidence interval for incremental costs and effects (gained disability adjusted life years - DALYs) and incremental cost-effectiveness ratios (ICER) were performed by Monte Carlo simulation with Ersatz software. RESULTS: ICER for screening programs with different TSH cut-off points versus no screening was similar, and approximately -4.5 ± 0.2 thousand US dollars per gained DALY. In the proposed cohort (10,000 neonates), gained DALYs were 316 ± 50 for a cut off point of 5 mU/l, 251 ± 40 for 10 mU/l, 146 ± 23 for 15 mU/l, and 113 ± 18 for a cut-off point of 20 mU/l. Sensitivity analysis showed that the model remained the same when the input parameters were changed. CONCLUSION: This study demonstrates that the current threshold of TSH in the national CH screening program in terms of cost-effectiveness is the most appropriate threshold. However, more studies are needed to examine new strategies and methods to reduce recall rates and related consequences such as repeated thyroid testing in neonates.

PMID 22369300


Feasibility of neonatal dried blood spot retrieval amid evolving state policies (2009-2010): a Children's Oncology Group study

Paediatr Perinat Epidemiol. 2011 Nov;25(6):549-58. doi: 10.1111/j.1365-3016.2011.01228.x. Epub 2011 Aug 10.

Linabery AM, Slater ME, Spector LG, Olshan AF, Stork SK, Roesler MA, Reaman GH, Ross JA. Source Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, 55455, USA.


Dried blood spots (DBS) are collected uniformly from US newborns to test for metabolic and other disorders. Because evidence exists for prenatal origins of some diseases, DBS may provide unique prenatal exposure records. Some states retain residual DBS and permit their use in aetiological studies. The primary study aim was to assess the feasibility of obtaining residual DBS from state newborn screening programmes for paediatric and adolescent cancer patients nationwide with parental/subject consent/assent. Families of leukaemia and lymphoma patients aged ≤21 years diagnosed from 1998 to 2007 at randomly selected Children's Oncology Group institutions across the US were questioned (n = 947). Parents/guardians and patients aged ≥18 years were asked to release DBS to investigators in spring 2009. DBS were then requested from states. Overall, 299 families (32%) released DBS. Consenting/assenting patients were born in 39 US states and 46 DBS were obtained from five states; 124 DBS were unobtainable because patients were born prior to dates of state retention. State policies are rapidly evolving and there is ongoing discussion regarding DBS storage and secondary research uses. Currently, population-based DBS studies can be conducted in a limited number of states; fortunately, many have large populations to provide reasonably sized paediatric subject groups. © 2011 Blackwell Publishing Ltd.

PMID 21980944

The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States

Clin Biochem. 2011 Dec;44(17-18):1445-50. Epub 2011 Sep 21.

Adam BW, Hall EM, Sternberg M, Lim TH, Flores SR, O'Brien S, Simms D, Li LX, De Jesus VR, Hannon WH. Source Centers for Disease Control and Prevention, 4770 Buford Highway NE, Atlanta, GA 30341, USA.


OBJECTIVE: 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. DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Minimizing both humidity and temperature in DBS transportation and storage environments is essential to maintaining sample integrity. Copyright © 2011 The Canadian Society of Clinical Chemists. All rights reserved. PMID 21963384


Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection

JAMA. 2010 Apr 14;303(14):1375-82.

Boppana SB, Ross SA, Novak Z, Shimamura M, Tolan RW Jr, Palmer AL, Ahmed A, Michaels MG, Sánchez PJ, Bernstein DI, Britt WJ, Fowler KB; National Institute on Deafness and Other Communication Disorders CMV and Hearing Multicenter Screening (CHIMES) Study. Collaborators (58)

Source UAB Department of Pediatrics, CHB 114, 1600 Sixth Ave S, Birmingham, AL 35233, USA. Abstract CONTEXT: Reliable methods to screen newborns for congenital cytomegalovirus (CMV) infection are needed for identification of infants at increased risk of hearing loss. Since dried blood spots (DBS) are routinely collected for metabolic screening from all newborns in the United States, there has been interest in using DBS polymerase chain reaction (PCR)-based methods for newborn CMV screening. OBJECTIVE: To determine the diagnostic accuracy of DBS real-time PCR assays for newborn CMV screening. DESIGN, SETTING, AND PARTICIPANTS: Between March 2007 and May 2008, infants born at 7 US medical centers had saliva specimens tested by rapid culture for early antigen fluorescent foci. Results of saliva rapid culture were compared with a single-primer (March 2007-December 2007) and a 2-primer DBS real-time PCR (January 2008-May 2008). Infants whose specimens screened positive on rapid culture or PCR had congenital infection confirmed by the reference standard method with rapid culture testing on saliva or urine. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative likelihood ratios (LRs) of single-primer and 2-primer DBS real-time PCR assays for identifying infants with confirmed congenital CMV infection. RESULTS: Congenital CMV infection was confirmed in 92 of 20,448 (0.45%; 95% confidence interval [CI], 0.36%-0.55%) infants. Ninety-one of 92 infants had positive results on saliva rapid culture. Of the 11,422 infants screened using the single-primer DBS PCR, 17 of 60 (28%) infants had positive results with this assay, whereas, among the 9026 infants screened using the 2-primer DBS PCR, 11 of 32 (34%) screened positive. The single-primer DBS PCR identified congenital CMV infection with a sensitivity of 28.3% (95% CI, 17.4%-41.4%), specificity of 99.9% (95% CI, 99.9%-100%), positive LR of 803.7 (95% CI, 278.7-2317.9), and negative LR of 0.7 (95% CI, 0.6-0.8). The positive and negative predictive values of the single-primer DBS PCR were 80.9% (95% CI, 58.1%-94.5%) and 99.6% (95% CI, 99.5%-99.7%), respectively. The 2-primer DBS PCR assay identified infants with congenital CMV infection with a sensitivity of 34.4% (95% CI, 18.6%-53.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), positive LR of 3088.9 (95% CI, 410.8-23 226.7), and negative LR of 0.7 (95% CI, 0.5-0.8). The positive and negative predictive values of the 2-primer DBS PCR were 91.7% (95% CI, 61.5%-99.8%) and 99.8% (95% CI, 99.6%-99.9%), respectively. CONCLUSION: Among newborns, CMV testing with DBS real-time PCR compared with saliva rapid culture had low sensitivity, limiting its value as a screening test. Comment in JAMA. 2010 Jul 28;304(4):407; author reply 408. JAMA. 2010 Jul 28;304(4):407-8; author reply 408. JAMA. 2010 Apr 14;303(14):1425-6.

PMID 20388893


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. 2009 Jan;62(1):26-30.

Streetly A, Latinovic R, Hall K, Henthorn J. Source NHS Sickle Cell and Thalassaemia Screening Programme, King's College London School of Medicine, Division of Health and Social Care Research, London, UK.


Early results from the National Health Service Sickle Cell and Thalassaemia Screening programme covering the whole of England are reported following the implementation of the national newborn blood-spot screening programme. Of the 13 laboratories performing screening, 10 chose high-performance liquid chromatography as the first screen, with isoelectric focusing as the second confirmatory test. Screening results for April 2005 to March 2007 are presented and include data from all the laboratories screening newborns in England, and almost 1.2 million infants. The screen-positive results show a national birth prevalence of almost 1 in 2000. The birth prevalence in London is five times that of most of the rest of the country. Over 17,000 carriers have been identified. Approximately seven per 1000 samples are reported as post-transfusion with wide ethnic category variation. Given the prevalence of the conditions, and coverage by ethnicity, 3-4 screen-positive cases could be missed each year. National implementation of newborn screening in England has increased the number of children identified with sickle cell disease, in many areas almost doubling the workload. Underascertainment of the condition has allowed a downplaying of the scale of need. It may also have contributed to infant mortality rates in urban areas as babies died without a diagnosis or treatment. The value of a co-ordinated national approach to policy development and implementation is emphasised by the English experience. The programme provides a model for Europe as well as other countries with significant minority populations, such as Canada. Potentially it also offers important lessons for Africa where the World Health Organization is supporting the introduction of newborn screening.

PMID 19103854 [PubMed - indexed for MEDLINE] PMCID: PMC2603283

Fabry disease

(Fabry disease, Fabry's disease, Anderson-Fabry disease, Alpha-galactosidase A deficiency, Angiokeratoma corporis diffusum, Ceramide trihexosidosis, Ruiter-Pompen-Wyers syndrome, Sweeley-Klionsky disease) Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease.