scholarly journals Pilot study of expanded newborn screening for 573 genes related to severe diseases in China: results from 1173 newborns

2019 ◽  
Author(s):  
Xiaomei Luo ◽  
Yu Sun ◽  
Feng Xu ◽  
Jun Guo ◽  
Lin Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Newborn Screening ◽  
Genetic Variants ◽  
Metabolic Diseases ◽  
Thyroid Stimulating Hormone ◽  
Carnitine Deficiency ◽  
Negative Results ◽  
Expanded Newborn Screening ◽  
Next Generation Sequencing Ngs ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Background: Current newborn screening (NBS) in China is mainly aimed at detecting biochemical levels of metabolites in blood, which may generate false positive/negative results. Methods: We designed a next-generation sequencing (NGS) panel of 573 genes related to severe diseases and performed NBS for 1173 individuals, who had been screened for tandem mass spectrometry (MS/MS), phenylalanine (Phe), thyroid-stimulating hormone (TSH), 17-α-hydroxyprogesterone (17-OHP) and glucose-6-phosphate dehydrogenase (G6PD) as conducted in traditional biochemical NBS in September 2016. We compared their biochemical results with genetic variants and investigated the carrier frequencies of 77 genes related to disorders of MS/MS in these newborns. Results: Biochemical results showed that four newborns were positive for G6PD enzymatic assay (all males), the other biochemical values including MS/MS, Phe, TSH and 17-OHP were negative. Genetic analysis results showed that all the four newborns with positive G6PD values carried G6PD hemizygous mutations. Besides, NGS results revealed an individual (ID 84123) carrying two common SLC22A5 mutations (c.760C>T/p.R254* and c.1400C>G/p.S467C) in Chinese population which were verified in trans later, was biochemical negative in 2016. MS/MS results in June 2019 showed free carnitine deficiency, which was consistence with genetic analysis results. Carrier frequencies data suggested the top five genes with the highest carrier frequencies in these newborns were PAH (2.04%), ETFDH (1.24%), MMACHC (1.15%), SLC25A13 (0.98%), and GCDH (0.80%). Conclusion: Our study provides data that combine biochemical results with genetic variants in 1173 newborns. This is the first study that reveals carrier frequencies of 77 genes causing inherited metabolic diseases (IMDs) in China.

scholarly journals Pilot study of expanded newborn screening for 573 genes related to severe diseases in China: results from 1173 newborns

2019 ◽  
Author(s):  
Xiaomei Luo ◽  
Yu Sun ◽  
Feng Xu ◽  
Jun Guo ◽  
Lin Li ◽  
...  
Keyword(s):  
Pilot Study ◽  
Genetic Analysis ◽  
Newborn Screening ◽  
Genetic Variants ◽  
Metabolic Diseases ◽  
False Negative ◽  
Dried Blood Spots ◽  
Carnitine Deficiency ◽  
Chinese Patients ◽  
Inherited Metabolic Diseases

Abstract Background: Current newborn screening (NBS) in China is mainly aimed at detecting biochemical levels of metabolites in the blood, which may generate false positive/negative results. To explore whether next-generation sequencing (NGS) for dried blood spots can increase the detecting rate of genetic disorders, we carried out a pilot study using NGS in 1,173 newborns who had been tested by traditional NBS. With a focus on inherited metabolic diseases (IMDs), our team investigated the current frequencies of genes related to common inherited metabolic diseases in this cohort. Methods: We designed an NGS panel of 573 genes related to severe diseases and performed NBS in 1,173 individuals who had been screened by tandem mass spectrometry (MS/MS) as well as for phenylalanine (Phe), thyroid-stimulating hormone (TSH), 17-α-hydroxyprogesterone (17-OHP), and glucose-6-phosphate dehydrogenase (G6PD) abnormalities in a traditional biochemical NBS conducted in September 2016. We compared the biochemical results to the genetic variants and investigated the carrier frequencies of 77 genes related to disorders by MS/MS in these newborns.Results: The biochemical results showed that four newborns (all male) were positive for G6PD by enzymatic assay, while the other biochemical findings including MS/MS, Phe, TSH and 17-OHP were negative. Genetic analysis results revealed that all the four newborns with positive G6PD values harbored hemizygous G6PD mutations. The NGS results also revealed an individual (ID 84123) carrying two SLC22A5 mutations (c.760C>T/p.R254* and c.1400C>G/p.S467C) common in Chinese patients with carnitine deficiency, which were later verified to be in trans, who was biochemically negative in 2016. The MS/MS results in 2019 showed free carnitine deficiency, consistent with the genetic analysis findings. The top five genes with the highest carrier frequencies in these newborns were PAH (1.77%), ETFDH (1.24%), MMACHC (1.15%), SLC25A13 (0.98%), and GCDH (0.80%). Conclusions: Our study provided data combing biochemical results with genetic variants in 1,173 newborns and confirmed a primary carnitine deficiency patient with false-negative biochemical results. This is also the first study to report the carrier frequencies of 77 IMD-causing genes in China.

scholarly journals Pilot study of expanded newborn screening for 573 genes related to severe diseases in China: results from 1173 newborns

2019 ◽  
Author(s):  
Xiaomei Luo ◽  
Yu Sun ◽  
Feng Xu ◽  
Jun Guo ◽  
Lin Li ◽  
...  
Keyword(s):  
Pilot Study ◽  
Genetic Analysis ◽  
Newborn Screening ◽  
Genetic Variants ◽  
Metabolic Diseases ◽  
False Negative ◽  
Dried Blood Spots ◽  
Carnitine Deficiency ◽  
Chinese Patients ◽  
Inherited Metabolic Diseases

Abstract Background: Current newborn screening (NBS) in China is mainly aimed at detecting biochemical levels of metabolites in the blood, which may generate false positive/negative results. To explore whether next-generation sequencing (NGS) for dried blood spots can increase the detecting rate, we carried out a pilot study using NGS in 1,173 newborns who had been tested by traditional NBS. With a focus on inherited metabolic diseases (IMDs), our team investigated the current frequencies of genes related to common inherited metabolic diseases in this cohort. Methods: We designed an NGS panel of 573 genes related to severe diseases and performed NBS in 1,173 individuals who had been screened by tandem mass spectrometry (MS/MS) as well as for phenylalanine (Phe), thyroid-stimulating hormone (TSH), 17-α-hydroxyprogesterone (17-OHP), and glucose-6-phosphate dehydrogenase (G6PD) abnormalities in a traditional biochemical NBS conducted in September 2016. We compared the biochemical results to the genetic variants and investigated the carrier frequencies of 77 genes related to disorders by MS/MS in these newborns.Results: The biochemical results showed that four newborns (all male) were positive for G6PD by enzymatic assay, while the other biochemical findings including MS/MS, Phe, TSH and 17-OHP were negative. Genetic analysis results revealed that all the four newborns with positive G6PD values harbored hemizygous G6PD mutations. The NGS results also revealed an individual (ID 84123) carrying two SLC22A5 mutations (c.760C>T/p.R254* and c.1400C>G/p.S467C) common in Chinese patients with carnitine deficiency, which were later verified to be in trans, who was biochemically negative in 2016. The MS/MS results in 2019 showed free carnitine deficiency, consistent with the genetic analysis findings. The top five genes with the highest carrier frequencies in these newborns were PAH (1.77%), ETFDH (1.24%), MMACHC (1.15%), SLC25A13 (0.98%), and GCDH (0.80%). Conclusions: Our study provided data combing biochemical results with genetic variants in 1,173 newborns and confirmed a primary carnitine deficiency patient with false-negative biochemical results. This is also the first study to report the carrier frequencies of 77 IMD-causing genes in China.

scholarly journals Newborn Screening for Congenital Hypothyroidism, Congenital Adrenal Hyperplasia, and Glucose-6-Phosphate Dehydrogenase Deficiency for Improving Health Care in India

2019 ◽  
Vol 09 (01) ◽  
pp. 040-044 ◽  
Author(s):  
Jyotsna Verma ◽  
Papai Roy ◽  
Divya C. Thomas ◽  
Geetu Jhingan ◽  
Azad Singh ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Newborn Screening ◽  
Congenital Hypothyroidism ◽  
G6pd Deficiency ◽  
Screening Program ◽  
Thyroid Stimulating Hormone ◽  
Adverse Outcomes ◽  
Adrenal Hyperplasia ◽  
Birth Prevalence ◽  
Glucose 6 Phosphate Dehydrogenase

AbstractNewborn screening (NBS) aims toward early detection of treatable congenital disorders. From January 2008 through December 2017, 13,376 newborns were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and glucose-6-phosphate dehydrogenase (G6PD) deficiency at Sir Ganga Ram Hospital, India, by measuring G6PD activity, thyroid-stimulating hormone, and 17-hydroxyprogesterone on dried blood specimens. The birth prevalence of 1:2,000 for CH, 1:2,500 for CAH, and 1:125 for G6PD deficiency indicates the latter as the most prevalent. Performance evaluation of testing reveals a robust screening program with 100% sensitivity and >99% specificity. Hence, we recommend NBS for early diagnosis and treatment to prevent adverse outcomes.

scholarly journals Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

2011 ◽  
Vol 6 (1) ◽  
pp. 44 ◽  
Author(s):  
Martin Lindner ◽  
Gwendolyn Gramer ◽  
Gisela Haege ◽  
Junmin Fang-Hoffmann ◽  
Karl O Schwab ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Metabolic Diseases ◽  
West Germany ◽  
South West ◽  
Expanded Newborn Screening

scholarly journals Primary carnitine deficiency – diagnosis after heart transplantation: Better late than never!

2020 ◽  
Author(s):  
Sarah Catharina Grünert ◽  
Sara Tucci ◽  
Anke Schumann ◽  
Meike Schwendt ◽  
Gwendolyn Gramer ◽  
...  
Keyword(s):  
Pilot Study ◽  
Heart Transplantation ◽  
Newborn Screening ◽  
Cardiac Death ◽  
Clinical Symptoms ◽  
Carnitine Deficiency ◽  
Carnitine Supplementation ◽  
Expanded Newborn Screening ◽  
Patients At Risk ◽  
Primary Carnitine Deficiency

Abstract Background Primary carnitine deficiency due to mutations in the OCTN2 gene is a rare but well-treatable metabolic disorder that puts patients at risk for metabolic decompensations, skeletal and cardiac myopathy and sudden cardiac death. Results We report on a 7-year-old boy diagnosed with primary carnitine deficiency 2 years after successful heart transplantation thanks his younger sister’s having been identified via expanded newborn screening during a pilot study evaluating an extension of the German newborn screening panel. Conclusion As L-carnitine supplementation can prevent and mostly reverse clinical symptoms of primary carnitine deficiency, all patients with cardiomyopathy should be investigated for primary carnitine deficiency even if newborn screening results were unremarkable.

Transient Neonatal Hypothyroidism Detected by Newborn Screening Program

PEDIATRICS ◽  
1977 ◽  
Vol 60 (4) ◽  
pp. 538-541
Author(s):  
STEPHEN H. LAFRANCHI ◽  
NEIL R. M. BUIST ◽  
WILLIAM H. MURPHEY ◽  
P. REED LARSEN ◽  
THOMAS P. FOLEY
Keyword(s):  
Newborn Screening ◽  
Filter Paper ◽  
Metabolic Diseases ◽  
Screening Program ◽  
Newborn Infants ◽  
Thyroid Stimulating Hormone ◽  
Newborn Screening Program ◽  
Neonatal Hypothyroidism ◽  
Blood Samples ◽  
Stimulating Hormone

A screening program for the detection of neonatal hypothyroidism has been in effect in Oregon since May 1975. Blood samples are obtained from all newborn infants to test for phenylketonuria and other metabolic diseases. A second specimen is obtained from more than 90% of these infants who are retested at 4 to 6 weeks of age. These Guthrie filter paper blood samples are analyzed for thyroxine (T4), and all samples with a low T4 value are analyzed for thyroid stimulating hormone (TSH). At the outset of the program, it was speculated that the screening might detect infants who had reduced

scholarly journals Very Long-Chain Acyl-CoA Dehydrogenase Deficiency: High Incidence of Detected Patients With Expanded Newborn Screening Program

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziga I. Remec ◽  
Urh Groselj ◽  
Ana Drole Torkar ◽  
Mojca Zerjav Tansek ◽  
Vanja Cuk ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Pilot Study ◽  
Genetic Analysis ◽  
Newborn Screening ◽  
Dehydrogenase Deficiency ◽  
Screening Program ◽  
Dried Blood Spots ◽  
Expanded Newborn Screening ◽  
Chain Acyl ◽  
Long Chain

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare autosomal recessive disorder of fatty acid metabolism with a variable presentation. The aim of this study was to describe five patients with VLCADD diagnosed through the pilot study and expanded newborn screening (NBS) program that started in 2018 in Slovenia. Four patients were diagnosed through the expanded NBS program with tandem mass spectrometry; one patient was previously diagnosed in a pilot study preceding the NBS implementation. Confirmatory testing consisted of acylcarnitines analysis in dried blood spots, organic acids profiling in urine, genetic analysis of ACADVL gene, and enzyme activity determination in lymphocytes or fibroblasts. Four newborns with specific elevation of acylcarnitines diagnostic for VLCADD and disease-specific acylcarnitines ratios (C14:1, C14, C14:2, C14:1/C2, C14:1/C16) were confirmed with genetic testing: all were compound heterozygotes, two of them had one previously unreported ACDVL gene variant each (NM_000018.3) c.1538C > G; (NP_000009) p.(Ala513Gly) and c.661A > G; p.(Ser221Gly), respectively. In addition, one patient diagnosed in the pilot study also had a specific elevation of acylcarnitines. Subsequent ACDVL genetic analysis confirmed compound heterozygosity. In agreement with the diagnosis, enzyme activity was reduced in five patients tested. In seven other newborns with positive screening results, only single allele variants were found in the ACDVL gene, so the diagnosis was not confirmed. Among these, two variants were novel, c.416T > C and c.1046C > A, respectively (p.Leu139Pro and p.Ala349Glu). In the first 2 years of the expanded NBS program in Slovenia altogether 30,000 newborns were screened. We diagnosed four cases of VLCADD. The estimated VLCADD incidence was 1:7,500 which was much higher than that of the medium-chain acyl-CoA dehydrogenase deficiency (MCADD) cases in the same period. Our study also provided one of the first descriptions of ACADVL variants in Central-Southeastern Europe and reported on 4 novel variants.

scholarly journals Primary carnitine deficiency – diagnosis after heart transplantation: Better late than never!

2020 ◽  
Author(s):  
Sarah Catharina Grünert ◽  
Sara Tucci ◽  
Anke Schumann ◽  
Meike Schwendt ◽  
Gwendolyn Gramer ◽  
...  
Keyword(s):  
Pilot Study ◽  
Heart Transplantation ◽  
Newborn Screening ◽  
Cardiac Death ◽  
Clinical Symptoms ◽  
Carnitine Deficiency ◽  
Carnitine Supplementation ◽  
Expanded Newborn Screening ◽  
Patients At Risk ◽  
Primary Carnitine Deficiency

Abstract Background Primary carnitine deficiency due to mutations in the OCTN2 gene is a rare but well-treatable metabolic disorder that puts patients at risk for metabolic decompensations, skeletal and cardiac myopathy and sudden cardiac death. Results We report on a 7-year-old boy diagnosed with primary carnitine deficiency 2 years after successful heart transplantation thanks his younger sister’s having been identified via expanded newborn screening during a pilot study evaluating an extension of the German newborn screening panel. Conclusion As L-carnitine supplementation can prevent and mostly reverse clinical symptoms of primary carnitine deficiency, all patients with cardiomyopathy should be investigated for primary carnitine deficiency even if newborn screening results were unremarkable.

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