Newborn Screening for Pompe Disease in Illinois: Experience with 684,290 Infants

Burton, Barbara K.; Charrow, Joel; Hoganson, George; Fleischer, Julie; Grange, Dorothy K.; Braddock, Stephen R.; Hitchins, Lauren; Hickey, Rachel; Christensen, Katherine; Groepper, Daniel; Shryock, Heather; Smith, P. Brian; Shao, Rong; Basheeruddin, Khaja

doi:10.3390/ijns6010004

Cited by 22 publications

(27 citation statements)

References 18 publications

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“…Newborn screening detects all subtypes of Pompe disease. The reported incidence of the disease has increased since initiation of NBS, with values ranging from 1:8684 to 1:23,596 [ 23 , 26 , 27 ]. Increased incidence is largely due to improved detection of LOPD and suspected LOPD cases through NBS.…”

Section: Discussionmentioning

confidence: 99%

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Newborn Screening for Pompe Disease: Pennsylvania Experience

Fıçıcıoğlu

Ahrens‐Nicklas

Joshua

et al. 2020

IJNS

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Pennsylvania started newborn screening for Pompe disease in February 2016. Between February 2016 and December 2019, 531,139 newborns were screened. Alpha-Glucosidase (GAA) enzyme activity is measured by flow-injection tandem mass spectrometry (FIA/MS/MS) and full sequencing of the GAA gene is performed as a second-tier test in all newborns with low GAA enzyme activity [<2.10 micromole/L/h]. A total of 115 newborns had low GAA enzyme activity and abnormal genetic testing and were referred to metabolic centers. Two newborns were diagnosed with Infantile Onset Pompe Disease (IOPD), and 31 newborns were confirmed to have Late Onset Pompe Disease (LOPD). The incidence of IOPD + LOPD was 1:16,095. A total of 30 patients were compound heterozygous for one pathogenic and one variant of unknown significance (VUS) mutation or two VUS mutations and were defined as suspected LOPD. The incidence of IOPD + LOPD + suspected LOPD was 1: 8431 in PA. We also found 35 carriers, 15 pseudodeficiency carriers, and 2 false positive newborns.

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Section: Discussionmentioning

confidence: 99%

“…Pennsylvania data differ from those of Illinois and Missouri. In Illinois, a total of 684,290 infants were screened between 3 November 2014 and 30 September 2019 [ 27 ]. A total of 395 newborns with positive NBS were referred to metabolic centers.…”

Section: Discussionmentioning

confidence: 99%

Newborn Screening for Pompe Disease: Pennsylvania Experience

Fıçıcıoğlu

Ahrens‐Nicklas

Joshua

et al. 2020

IJNS

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“…Targeted NGS could reduce the treatment delay for those identified by PD screening by allowing analysis, interpretation, and appropriate reporting of healthcare related information in a timely manner. Already several PHLs in the USA have adopted second tier tNGS in-house or as a service [26,27]. New York and California PHLs have strong DNA sequencing second tier programs including tNGS for PD and other NBS disorders.…”

Section: Current and Future Utilization Of Tngs Testingmentioning

confidence: 99%

Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges

Smith

Bainbridge

Parad

et al. 2020

IJNS

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Pompe disease (PD) is screened by a two tier newborn screening (NBS) algorithm, the first tier of which is an enzymatic assay performed on newborn dried blood spots (DBS). As first tier enzymatic screening tests have false positive results, an immediate second tier test on the same sample is critical in resolving newborn health status. Two methodologies have been proposed for second tier testing: (a) measurement of enzymatic activities such as of Creatine/Creatinine over alpha-glucosidase ratio, and (b) DNA sequencing (a molecular genetics approach), such as targeted next generation sequencing. (tNGS). In this review, we discuss the tNGS approach, as well as the challenges in providing second tier screening and follow-up care. While tNGS can predict genotype-phenotype effects when known, these advantages may be diminished when the variants are novel, of unknown significance or not discoverable by current test methodologies. Due to the fact that criticisms of screening algorithms that utilize tNGS are based on perceived complexities, including variant detection and interpretation, we clarify the actual limitations and present the rationale that supports optimizing a molecular genetic testing approach with tNGS. Second tier tNGS can benefit clinical decision-making through the use of the initial NBS DBS punch and rapid turn-around time methodology for tNGS, that includes copy number variant analysis, variant effect prediction, and variant ‘cut-off’ tools for the reduction of false positive results. The availability of DNA sequence data will contribute to the improved understanding of genotype-phenotype associations and application of treatment. The ultimate goal of second tier testing should enable the earliest possible diagnosis for the earliest initiation of the most effective clinical interventions in infants with PD.

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“…Infants with only pseudodeficiency allele/s 2. Most of the infants in this category had VUS and two pseudodeficiency alleles 3. Infants in this category had one pathogenic variant, or one VUS, with or without pseudodeficiency alleles classified as carriers.…”

mentioning

confidence: 93%

“…The State of Illinois initiated newborn screening (NBS) for Krabbe disease (KD; globoid cell leukodystrophy; OMIM 245200) in December 2017 by measuring galactocerebrosidase (GALC; EC 3.2.1.46) activity in dried blood spots (DBSs). The statewide screening program includes the measurement of seven lysosomal enzymes to screen for lysosomal storage diseases (LSDs) using tandem mass spectrometry [1][2][3]. Pompe disease and Mucopolysaccharidosis I (MPS I) are the only two lysosomal diseases included on the federal Recommended Uniform Newborn Screening Panel (RUSP) by the Advisory Committee on Heritable Disorders in Newborns and Children of the Department of Health and Human Services.…”

Section: Introductionmentioning

confidence: 99%

Newborn Screening for Krabbe Disease—Illinois Experience: Role of Psychosine in Diagnosis of the Disease

Basheeruddin

Shao

Balster

et al. 2021

IJNS

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Population-based newborn screening for Krabbe disease was initiated by measurement of galactocerebrosidase (GALC) activity in the state of Illinois in December 2017. Due to the poor specificity of GALC for the diagnosis of Krabbe disease, second-tier testing services were provided to reduce the false positive rates for disease monitoring. Using ultra-pressure liquid chromatography coupled to mass spectrometry assay, a total of 497,147 newborns were screened. In total, 288 infants’ specimens (0.06%) having reduced GALC activity were sent out for second-tier testing to a reference laboratory. All newborns’ reduced GALC specimens were tested for psychosine levels, the presence of a 30-kb deletion and GALC sequencing. The results showed that two infants had elevated psychosine levels (10 and 35 nM) and were referred immediately for evaluation and treatment for Infantile Krabbe disease, and six infants had intermediate PSY levels (≥2 to 5 nM) and are under observation as suspected candidates for late-onset Krabbe disease. In addition, 178 infants had pseudodeficiency alleles, all having psychosine levels < 2.0 nM. Our data show that a high percentage of reduced GALC activity (62%) was due to the presence of pseudodeficiency alleles in the GALC gene. In conclusion, incorporation of psychosine measurements can identify infants with infantile Krabbe disease and probable late-onset Krabbe infants. Furthermore, Krabbe disease screening can be achieved at public health laboratories, and infants with infantile Krabbe disease can be diagnosed in timely manner for better outcome.

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Newborn Screening for Pompe Disease in Illinois: Experience with 684,290 Infants

Cited by 22 publications

References 18 publications

Newborn Screening for Pompe Disease: Pennsylvania Experience

Newborn Screening for Pompe Disease: Pennsylvania Experience

Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges

Newborn Screening for Krabbe Disease—Illinois Experience: Role of Psychosine in Diagnosis of the Disease

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