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Int. J. Neonatal Screen., Volume 3, Issue 1 (March 2017) – 5 articles

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6 pages, 306 KiB

Open AccessCase Report

A Rare Case of Malonic Aciduria Diagnosed by Newborn Screening in Qatar

by Mamatha Ramaswamy^1,*, Victor Anthony Skrinska¹, Ghassan Abdoh², Laila Mahmoud Ahmed³, Rola Fayez Mitri¹ and Ravi Joshi¹

¹ Metabolic Laboratory, Department of Pathology and Laboratory Medicine, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

² Newborn Screening Unit, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

³ Department of Paediatrics, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

Int. J. Neonatal Screen. 2017, 3(1), 5; https://doi.org/10.3390/ijns3010005 - 9 Mar 2017

Cited by 2 | Viewed by 7995

Abstract

Malonic aciduria is a rare autosomal recessive organic acid disorder. With the widespread use of tandem mass spectrometry for analysis of the amino acid/acylcarnitine profile on dried blood spots for newborn screening (NBS), this condition can be readily diagnosed and can be included in the organic acid screen in NBS programs. In Qatar, we report the first case of an asymptomatic baby screened and diagnosed with malonic aciduria through NBS. This patient has a genetic variant of malonyl-CoA decarboxylase that has not been previously reported in the literature. This condition should be differentiated from a similar disorder, combined malonic and methylmalonic aciduria. The clinical phenotype of malonic aciduria is variable and the pathophysiology is not fully understood. There is no established guidance or recommendations regarding the appropriate treatment regimen, dietary therapy or regular follow-up of these patients. Most available evidence for treatment is based on a single study or case report. Full article

(This article belongs to the Special Issue Newborn Screening-Past, Present and Future)

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4 pages, 180 KiB

Open AccessCase Report

The Risk from Anti-Thyroid Hormone Antibody Interference in Neonatal Congenital Hypothyroidism Screening

by Ian Brincat^* and Gerald Buhagiar

Clinical Chemistry Laboratory, Department of Pathology, Mater Dei Hospital, Malta

Int. J. Neonatal Screen. 2017, 3(1), 4; https://doi.org/10.3390/ijns3010004 - 2 Mar 2017

Cited by 1 | Viewed by 3555

Abstract

Neonatal congenital hypothyroidism screening is considered to be one of the most effective newborn screening strategies. Neonatal screening for congenital hypothyroidism involves the analysis of thyroid hormone and thyrotropin levels using an immunoassay based technique. Immunoassays are also prone to analytical problems such as assay interference. Immunoassays used for thyroid hormone measurement are known to be affected from anti-thyroid hormone antibody interference. This is the first reported case of interference presumably caused by anti-thyroid hormone antibodies transferred from mother to child during pregnancy, affecting the measurement of free-thyroxine in a cord-blood sample. We report a case of a full-term newborn with presumed anti-thyroid hormone antibody interference present in both cord blood and subsequent venous blood samples. In the context of a newborn screening programme based solely on thyroxine measurement, this is an important finding, since it has the potential to cause false negative screening results. Full article

14 pages, 246 KiB

Open AccessReview

Newborn Screening for Krabbe Disease and Other Lysosomal Storage Disorders: Broad Lessons Learned

by Joseph J. Orsini^* and Michele Caggana

Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, 12201-2002 NY, USA

Int. J. Neonatal Screen. 2017, 3(1), 3; https://doi.org/10.3390/ijns3010003 - 1 Mar 2017

Cited by 7 | Viewed by 5680

Abstract

Newborn screening (NBS) for Krabbe disease (KD) began in New York (NY) in August 2006. In summary, after eight years of screening there were five infants identified with early-onset Krabbe disease. Four underwent transplant, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. An additional forty-six asymptomatic infants were found to be at moderate or high risk for disease. Screening for KD is both analytically and medically challenging; since screening for KD possesses both of these challenges, and many more, the lessons learned thus far could be used to predict the challenges that may be faced when screening for other lysosomal storage disorders (LSDs). This paper briefly reviews reports of NBS for LSDs from varied world programs. The challenges encountered in screening for KD in NY will be highlighted, and this experience, combined with hindsight, will inform what may be expected in the future as screening for LSDs expands. Full article

(This article belongs to the Special Issue Newborn Screening-Past, Present and Future)

12 pages, 1104 KiB

Open AccessArticle

Fibroblast Fatty-Acid Oxidation Flux Assays Stratify Risk in Newborns with Presumptive-Positive Results on Screening for Very-Long Chain Acyl-CoA Dehydrogenase Deficiency

by Simon E. Olpin^1,*

, Shirley Clark¹, Jane Dalley¹, Brage S. Andresen², Joanne Croft¹, Camilla A. Scott¹, Aneal Khan³, Richard J. Kirk⁴, Rebecca Sparkes³, Marisa Chard³, Alicia Chan⁵, Emma Glamuzina⁶, Jean Bastin⁷, Nigel J. Manning¹ and Rodney J. Pollitt¹

¹ Department of Clinical Chemistry, Sheffield Children’s Hospital Sheffield, Sheffield S10 2TH, UK

² Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark

³ Department of Medical Genetics & Paediatrics, Alberta Children’s Hospital, Calgary, AB T3B 6A8, Canada

⁴ Department of Molecular Genetics, Sheffield Children’s Hospital, Sheffield S10 2TH, UK

⁵ Department of Medical Genetics, University of Alberta, Calgary, AB T3B 6A8, Canada

⁶ National Metabolic Service, Starship Children’s Hospital, Auckland 1042, New Zealand

⁷ Inserm U747, Université Paris Descartes, UFR Biomédicale des Saints-Pères, 75270 Paris CEDEX 06, France

Int. J. Neonatal Screen. 2017, 3(1), 2; https://doi.org/10.3390/ijns3010002 - 24 Feb 2017

Cited by 6 | Viewed by 6456

Abstract

Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD) is a clinically heterogeneous disorder with three major phenotypes: severe neonatal/infantile, milder childhood and late onset myopathic. VLCADD is genetically heterogeneous with numerous pathogenic mutations and variants of uncertain significance. VLCADD is included in many newborn screening programs but these suffer from high false positive rates, primarily due to positive screens in heterozygotes. Separating these and newborns with two low-risk “mild” variants from clinically at risk patients can be problematic, as clinical and biochemical markers are often unreliable, particularly in stable neonates. We have measured fibroblast fatty acid oxidation flux using [9,10-H³]myristic acid and [9,10-H³]oleic acid from 69 clinically presenting VLCADD patients including myopathic and infantile phenotypes and 13 positive newborn screened patients. We also measured fibroblast VLCADD enzyme activity by UV-HPLC detection of product in a sub-set of patients and compared these results to oleate FAO-flux. Fibroblast enzyme assay by UV-HPLC detection failed to clearly discriminate between some clinically presenting VLCADD patient cell lines and cell lines from some simple heterozygotes. FAO-flux clearly discriminated between clinically presenting VLCADD patients and the false positive screened patients. FAO-flux at 37 °C provides information as to the likely clinical phenotype but FAO-flux at 41 °C is the best discriminator for identifying clinically at risk patients. Full article

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10 pages, 872 KiB

Open AccessReview

Neonatal Screening for Primary Carnitine Deficiency: Lessons Learned from the Faroe Islands

by Ulrike Steuerwald^1,2,3, Allan M. Lund⁴, Jan Rasmussen¹, Nils Janzen^3,5

, David M. Hougaard⁶

and Nicola Longo^7,*

¹ Medical Department, National Hospital of the Faroe Islands, Tórshavn 100, Faroe Islands

² Department of Occupational Medicine and Public Health, National Hospital of the Faroe Islands, Tórshavn 100, Faroe Islands

³ Screening-Laboratory Hannover, POB 91 10 09, Hannover 30430, Germany

⁴ Department of Clinical Genetics, Centre for Inherited Metabolic Diseases, Copenhagen University Hospital, Copenhagen 2100, Denmark

⁵ Department of Clinical Chemistry, Medical School, Hannover 30625, Germany

⁶ Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen S 2300, Denmark

⁷ Division of Medical Genetics, Departments of Pediatrics and Pathology, and ARUP Laboratories, University of Utah, Salt Lake City, UT 84103, USA

Int. J. Neonatal Screen. 2017, 3(1), 1; https://doi.org/10.3390/ijns3010001 - 4 Feb 2017

Cited by 10 | Viewed by 10077

Abstract

Primary carnitine deficiency is caused by the defective OCTN2 carnitine transporter encoded by the SLC22A5 gene. A lack of carnitine impairs fatty acid oxidation resulting in hypoketotic hypoglycemia, hepatic encephalopathy, skeletal and cardiac myopathy, and arrhythmia. This condition can be detected by finding low levels of free carnitine (C0) in neonatal screening. Mothers with primary carnitine deficiency can also be identified by low carnitine levels in their infant by newborn screening. Primary carnitine deficiency is rare (1:40,000–1:140,000 newborns) except in the Faroe Islands (1:300) due to a founder effect. A specific mutation (c.95A>G, p.N32S) is prevalent, but not unique, with three additional mutations (c.131C>T/p.A44V, a splice mutation c.825-52G>A, and a risk-haplotype) recently identified in the Faroese population. In the Faroe Islands, several adult patients suffered sudden death from primary carnitine deficiency leading to the implementation of a nationwide population screening (performed after 2 months of age) in addition to universal neonatal screening. While most affected infants can be identified at birth, some patients with primary carnitine deficiency might be missed by the current neonatal screening and could be better identified with a repeated test performed after 2 months of age. Full article

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