scholarly journals Normal Levels of Plasma Free Carnitine and Acylcarnitines in Follow-Up Samples from a Presymptomatic Case of Carnitine Palmitoyl Transferase 1 (CPT1) Deficiency Detected Through Newborn Screening in Denmark

2011 ◽  
pp. 11-15 ◽  
Author(s):  
Luise Borch ◽  
Allan Meldgaard Lund ◽  
Flemming Wibrand ◽  
Ernst Christensen ◽  
Charlotte Søndergaard ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Free Carnitine ◽  
Carnitine Palmitoyl Transferase

scholarly journals Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Yi Gan ◽  
Fei Yu ◽  
Haining Fang
Keyword(s):  
Newborn Screening ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Carnitine Palmitoyltransferase ◽  
Free Carnitine ◽  
Dimensional Structure ◽  
Acid Oxidation ◽  
First Case ◽  
Mitochondrial Fatty Acid

Abstract Background Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been reported in China. Case presentation A newborn male, without any disease-related clinical manifestations, was diagnosed with CPT1A deficiency through newborn screening. Increased free carnitine levels and a significantly increased C0/(C16 + C18) ratio were detected by tandem mass spectrometry, and subsequently, mutations in CPT1A were found by gene sequence analysis. The patient was advised a low-fat, high-protein diet and followed up regularly. During three-years of follow-up since, the patient showed normal growth velocity and developmental milestones. Whole-exome sequence identified two mutations, c.2201 T > C (p.F734S) and c.1318G > A (p.A440T), in the patient. The c.2201 T > C mutation, which has been reported previously, was inherited from his father, while the c.1318G > A, a novel mutation, was inherited from his mother. The amino acid residues encoded by original sequences are highly conserved across different species. These mutations slightly altered the three-dimensional structure of the protein, as analyzed by molecular modeling, suggesting that they may be pathogenic. Conclusion This is the first case of CPT1A deficiency detected through newborn screening based on diagnostic levels of free carnitine, in China. Three years follow-up suggested that early diagnosis and diet management may improve the prognosis in CPT1A patient. In addition, we identified a novel mutation c.1318G > A in CPT1A,and a possible unique to Chinese lineage mutation c.2201 T > C. Our findings have expanded the gene spectrum of this rare condition and provided a basis for family genetic counseling and prenatal diagnosis.

scholarly journals Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

2021 ◽  
Vol 7 (2) ◽  
pp. 22
Author(s):  
Jamie Matteson ◽  
Stanley Sciortino ◽  
Lisa Feuchtbaum ◽  
Tracey Bishop ◽  
Richard S. Olney ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Program Implementation ◽  
Screening Program ◽  
Birth Prevalence ◽  
Variant Of Uncertain Significance ◽  
Implementation Challenges ◽  
Screening Programs ◽  
Uncertain Significance ◽  
Long Term Follow Up

X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California’s experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020. In the first four years of ALD newborn screening in California, 355 newborns screened positive for ALD, including 147 (41%) with an ABCD1 variant of uncertain significance (VUS) and 95 males diagnosed with ALD. After modifying cutoffs, we observed an ALD birth prevalence of 1 in 14,397 males. Long-term follow-up identified 14 males with signs of adrenal involvement. This study adds to a growing body of literature reporting on outcomes of newborn screening for ALD and offering a glimpse of what other large newborn screening programs can expect when adding ALD to their screening panel.

scholarly journals Mass Spectrometry but Not Fluorimetry Distinguishes Affected and Pseudodeficiency Patients in Newborn Screening for Pompe Disease

2017 ◽  
Vol 63 (7) ◽  
pp. 1271-1277 ◽  
Author(s):  
Hsuan-Chieh Liao ◽  
Min-Ju Chan ◽  
Chia-Feng Yang ◽  
Chuan-Chi Chiang ◽  
Dau-Ming Niu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Late Onset ◽  
Asian Population ◽  
Dried Blood Spots ◽  
Fluorimetric Assay ◽  
Analytical Range ◽  
Patient Referrals

Abstract BACKGROUND Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up. METHODS We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively large analytical range compared to the fluorimetric assay with 4-methylumbelliferyl-α-glucoside. DBS from newborns confirmed to have infantile-onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12) and those from patients bearing pseudodeficiency alleles with or without Pompe mutations, or Pompe disease carriers (n = 230) were studied. RESULTS With use of the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the Pompe disease carriers were well separated from the IOPD and LOPD newborns. The fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD group. CONCLUSIONS The relatively large analytical range MS/MS GAA assay but not the fluorimetric assay in DBS provides a robust approach to reduce the number of referrals and should dramatically facilitate newborn screening of Pompe disease.

Newborn Screening for Cystic Fibrosis

PEDIATRICS ◽  
1991 ◽  
Vol 87 (6) ◽  
pp. 954-955
Author(s):  
IAN C. T. LYON ◽  
DIANNE R. WEBSTER
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Elevated Level ◽  
Meconium Ileus ◽  
Screening Tests ◽  
Initial Screening ◽  
False Negatives ◽  
Immunoreactive Trypsinogen

To the Editor.— The report on newborn screening for cystic fibrosis1 illustrates the need for continued evaluation of such programs. The authors state that the identification of cases of cystic fibrosis (CF) by an elevated level of immunoreactive trypsinogen (IRT) in second (follow-up) samples from infants with positive initial screening tests could result in false negatives in 27% of cases of cystic fibrosis without meconium ileus (MI). We have screened 401 122 infants using the method originally reported.2

Long-term follow-up of newborn screening patients

2010 ◽  
Vol 12 ◽  
pp. S267-S268 ◽  
Author(s):  
Susan A. Berry ◽  
Michele A. Lloyd-Puryear ◽  
Michael S. Watson
Keyword(s):  
Newborn Screening ◽  
Long Term Follow Up

scholarly journals Long-term follow-up to ensure quality care of individuals diagnosed with newborn screening conditions: Early experience in New England

2010 ◽  
Vol 12 ◽  
pp. S220-S227 ◽  
Author(s):  
Inderneel Sahai ◽  
Roger B. Eaton ◽  
Jaime E. Hale ◽  
Eleanor A. Mulcahy ◽  
Anne Marie Comeau
Keyword(s):  
Newborn Screening ◽  
New England ◽  
Quality Care ◽  
Early Experience ◽  
Long Term Follow Up

scholarly journals Immunoreactive Trypsinogen and Free Carnitine Changes on Newborn Screening after Birth in Patients Who Develop Type 1 Diabetes

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3669
Author(s):  
Jane Frances Grace Lustre Estrella ◽  
Veronica C. Wiley ◽  
David Simmons
Keyword(s):  
Type 1 Diabetes ◽  
Newborn Screening ◽  
Conditional Logistic Regression ◽  
Free Carnitine ◽  
Parameter Estimates ◽  
Reference Ranges ◽  
Develop Type ◽  
Post Hoc ◽  
Immunoreactive Trypsinogen

Are free carnitine concentrations on newborn screening (NBS) 48–72 h after birth lower in patients who develop type 1 diabetes than in controls? A retrospective case-control study of patients with type 1 diabetes was conducted. NBS results of patients from a Sydney hospital were compared against matched controls from the same hospital (1:5). Multiple imputation was performed for estimating missing data (gestational age) using gender and birthweight. Conditional logistic regression was used to control for confounding and to generate parameter estimates (α = 0.05). The Hommel approach was used for post-hoc analyses. Results are reported as medians and interquartile ranges. A total of 159 patients were eligible (80 females). Antibodies were detectable in 86. Median age at diagnosis was 8 years. Free carnitine concentrations were lower in patients than controls (25.50 µmol/L;18.98–33.61 vs. 27.26; 21.22–34.86 respectively) (p = 0.018). Immunoreactive trypsinogen was higher in this group (20.24 µg/L;16.15–29–52 vs. 18.71; 13.96–26.92) (p = 0.045), which did not persist in the post-hoc analysis. Carnitine levels are lower and immunoreactive trypsinogen might be higher, within 2–3 days of birth and years before development of type 1 diabetes as compared to controls, although the differences were well within reference ranges and provide insight into the pathogenesis into neonatal onset of type 1 diabetes development rather than use as a diagnostic tool. Given trypsinogen’s use for evaluation of new-onset type 1 diabetes, larger studies are warranted.

scholarly journals National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Follow-Up Testing for Metabolic Disease Identified by Expanded Newborn Screening Using Tandem Mass Spectrometry; Executive Summary

2009 ◽  
Vol 55 (9) ◽  
pp. 1615-1626 ◽  
Author(s):  
Dennis J Dietzen ◽  
Piero Rinaldo ◽  
Ronald J Whitley ◽  
William J Rhead ◽  
W Harry Hannon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amino Acids ◽  
Tandem Mass Spectrometry ◽  
Organic Acids ◽  
Newborn Screening ◽  
Tandem Mass ◽  
Confirmatory Testing ◽  
The Us ◽  
The Impact

Abstract Background: Almost all newborns in the US are screened at birth for multiple inborn errors of metabolism using tandem mass spectrometry. Screening tests are designed to be sufficiently sensitive so that cases are not missed. The NACB recognized a need for standard guidelines for laboratory confirmation of a positive newborn screen such that all babies would benefit from equal and optimal follow-up by confirmatory testing. Methods: A committee was formed to review available data pertaining to confirmatory testing. The committee evaluated previously published guidelines, published methodological and clinical studies, clinical case reports, and expert opinion to support optimal confirmatory testing. Grading was based on guidelines adopted from criteria derived from the US Preventive Services Task Force and on the strength of recommendations and the quality of the evidence. Three primary methods of analyte measurement were evaluated for confirmatory testing including measurement of amino acids, organic acids, and carnitine esters. The committee graded the evidence for diagnostic utility of each test for the screened conditions. Results: Ample data and experience were available to make strong recommendations for the practice of analyzing amino acids, organic acids, and acylcarnitines. Likewise, strong recommendations were made for the follow-up test menu for many disorders, particularly those with highest prevalence. Fewer data exist to determine the impact of newborn screening on patient outcomes in all but a few disorders. The guidelines also provide an assessment of developing technology that will fuel a refinement of current practice and ultimate expansion of the diseases detectable by tandem mass spectrometry. Conclusions: Guidelines are provided for optimal follow-up testing for positive newborn screens using tandem mass spectrometry. The committee regards these tests as reliable and currently optimal for follow-up testing. .

scholarly journals Implementing a tracking system for confirmatory diagnostic results after positive newborn screening for cystic fibrosis—implications for process quality and patient care

2020 ◽  
Author(s):  
Gwendolyn Gramer ◽  
Inken Brockow ◽  
Christiane Labitzke ◽  
Junmin Fang-Hoffmann ◽  
Andreas Beivers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Patient Care ◽  
Tracking System ◽  
Process Quality ◽  
Federal State ◽  
Cost Calculation ◽  
Confirmatory Testing ◽  
Before And After

Abstract Newborn screening for cystic fibrosis (CF-NBS) was introduced in Germany in 2016. Currently, systematic follow-up of positive CF-NBS results is not implemented or reimbursed in the NBS program. We investigated results of confirmatory testing over 24 months after implementation of CF-NBS for a large German NBS center before and after introduction of an active tracking system and performed a cost calculation for tracking. Results are compared with the federal state of Bavaria, where a centralized tracking system has been in place for many years. At the NBS center, 244 of 281,907 children had a positive CF-NBS result requiring diagnostic confirmation. Before implementation of a telephone tracking system, only 43% of confirmatory results were returned despite repeated written requests. The consecutive strategy including telephone tracking led to an increase of resolved cases to 84%. However, the centralized tracking system in Bavaria, assigning children with positive CF-NBS directly to a responsible CF-center, resolved 99% of cases. The calculated additional cost for a tracking system in Germany including telephone tracking is 1.20€ per newborn screened. Conclusion: The implementation of a tracking system achieves a distinct improvement in CF-NBS with justifiable costs. The effect can be limited by absence of centralized organization of confirmatory testing. What is Known:• Newborn screening for cystic fibrosis (CF-NBS) has been performed for many years in several countries worldwide• While many studies have focused on different CF-NBS strategies, the organization of confirmatory testing and process quality concerning returned information to the NBS center has so far received less attention. What is New:• The implementation of an active tracking system achieves a distinct improvement of clarified cases after positive CF-NBS with justifiable costs.• The effect of a tracking system can be limited by the absence of a centralized organization of confirmatory testing.

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