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

2020 ◽  
Vol 6 (1) ◽  
pp. 4 ◽  
Author(s):  
Barbara K. Burton ◽  
Joel Charrow ◽  
George E. Hoganson ◽  
Julie Fleischer ◽  
Dorothy K. Grange ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Pompe Disease ◽  
Late Onset ◽  
Definitive Diagnosis ◽  
Glucosidase Activity ◽  
Alpha Glucosidase

Statewide newborn screening for Pompe disease began in Illinois in 2015. As of 30 September 2019, a total of 684,290 infants had been screened and 395 infants (0.06%) were screen positive. A total of 29 cases of Pompe disease were identified (3 infantile, 26 late-onset). While many of the remainder were found to have normal alpha-glucosidase activity on the follow-up testing (234 of 395), other findings included 62 carriers, 39 infants with pseudodeficiency, and eight infants who could not be given a definitive diagnosis due to inconclusive follow-up testing.

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.

scholarly journals Newborn Screening for Pompe Disease: Pennsylvania Experience

2020 ◽  
Vol 6 (4) ◽  
pp. 89
Author(s):  
Can Ficicioglu ◽  
Rebecca C. Ahrens-Nicklas ◽  
Joshua Barch ◽  
Sanmati R. Cuddapah ◽  
Brenda S. DiBoscio ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Late Onset ◽  
Compound Heterozygous ◽  
Variant Of Unknown Significance ◽  
Unknown Significance ◽  
Second Tier ◽  
Alpha Glucosidase ◽  
Gaa Gene

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.

scholarly journals Splice modulating antisense oligonucleotides restore some acid-alpha-glucosidase activity in cells derived from patients with late-onset Pompe disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
May Thandar Aung-Htut ◽  
Kristin A. Ham ◽  
Michel Tchan ◽  
Russell Johnsen ◽  
Frederick J. Schnell ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Antisense Oligonucleotides ◽  
Late Onset ◽  
Glucosidase Activity ◽  
Alpha Glucosidase ◽  
In Cells

scholarly journals Current status of newborn screening for Pompe disease in Japan

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takaaki Sawada ◽  
Jun Kido ◽  
Keishin Sugawara ◽  
Ken Momosaki ◽  
Shinichiro Yoshida ◽  
...  
Keyword(s):  
United States ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Autosomal Recessive ◽  
Late Onset ◽  
The United States ◽  
Current Status ◽  
Inherited Metabolic Disorder ◽  
Enzyme Replacement

Abstract Background Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease. Results From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years. Conclusions The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.

scholarly journals Current Status of Newborn Screening for Pompe Disease in Japan

2021 ◽  
Author(s):  
Takaaki Sawada ◽  
Jun Kido ◽  
Keishin Sugawara ◽  
Ken Momosaki ◽  
Shinichiro Yoshida ◽  
...  
Keyword(s):  
United States ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Autosomal Recessive ◽  
Late Onset ◽  
The United States ◽  
Current Status ◽  
Inherited Metabolic Disorder ◽  
Enzyme Replacement

Abstract Background: Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (AαGlu). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease.Results: From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years.Conclusions: The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan.

scholarly journals M Mode Ultrasound and Tissue Doppler Imaging to Assess Diaphragm Function in Late Onset Pompe Disease

2020 ◽  
Author(s):  
Paris Meng ◽  
Adam Ogna ◽  
Abdallah Fayssoil
Keyword(s):  
Tissue Doppler Imaging ◽  
Pompe Disease ◽  
Skeletal Muscles ◽  
Storage Disease ◽  
Late Onset ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Lysosomal Storage ◽  
Diaphragm Function

Late onset Pompe disease is a recessive lysosomal storage disease. Clinical features include skeletal muscles deficiency and diaphragm weakness. Clinical management relies on supportive treatment and mechanical ventilation in patents with chronic respiratory failure. M mode ultrasound and tissue Doppler imaging can be used to assess and to follow up diaphragm function.

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