scholarly journals A Newborn Screening, Presymptomatically Identified Infant With Late-Onset Pompe Disease: Case Report, Parental Experience, and Recommendations

2020 ◽  
Vol 6 (1) ◽  
pp. 22
Author(s):  
Raymond Y. Wang
Keyword(s):  
Newborn Screening ◽  
Respiratory Insufficiency ◽  
Pompe Disease ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Lysosomal Storage ◽  
Parental Experience ◽  
Screening Programs ◽  
Disease Case ◽  
Newborn Screen

Pompe disease is an inherited lysosomal storage disorder caused by acid alpha-glucosidase (GAA) enzyme deficiency, resulting in muscle and neuron intralysosomal glycogen storage. Clinical symptoms vary from the severe, infantile-onset form with hypertrophic cardiomyopathy, gross motor delay, and early death from respiratory insufficiency; to a late-onset form with variable onset of proximal muscle weakness and progressive respiratory insufficiency. Newborn screening programs have been instituted to presymptomatically identify neonates with infantile-onset Pompe disease for early initiation of treatment. However, infants with late-onset Pompe disease are also identified, leaving families and physicians in a state of uncertainty regarding prognosis, necessity, and timing of treatment initiation. This report presents a 31 5/7 weeks’ gestational age premature infant flagged positive for Pompe disease with low dried blood spot GAA activity; sequencing identified biparental c.-32-13T>G/c.29delA GAA variants predicting late-onset Pompe disease. The infant’s parents’ initial reactions to the positive newborn screen, subsequent experience during confirmatory testing, and post-confirmation reflections are also reported. While uncertainties regarding natural history and prognosis of presymptomatically-identified late-onset Pompe disease infants will be elucidated with additional experience, suggestions for education of first-line providers are provided to accurately communicate results and compassionately counsel families regarding anxiety-provoking positive newborn screen results.

scholarly journals Liquid Chromatography–Tandem Mass Spectrometry Assay of Leukocyte Acid α-Glucosidase for Post-Newborn Screening Evaluation of Pompe Disease

2017 ◽  
Vol 63 (4) ◽  
pp. 842-851 ◽  
Author(s):  
Na Lin ◽  
Jingyu Huang ◽  
Sara Violante ◽  
Joseph J Orsini ◽  
Michele Caggana ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Pompe Disease ◽  
Late Onset ◽  
Treatment Options ◽  
Internal Standard ◽  
Lysosomal Storage ◽  
Blood Samples ◽  
Liquid Chromatography Tandem Mass ◽  
Progressive Weakness

Abstract BACKGROUND Pompe disease (PD) is the first lysosomal storage disorder to be added to the Recommended Uniform Screening Panel for newborn screening. This condition has a broad phenotypic spectrum, ranging from an infantile form (IOPD), with severe morbidity and mortality in infancy, to a late-onset form (LOPD) with variable onset and progressive weakness and respiratory failure. Because the prognosis and treatment options are different for IOPD and LOPD, it is important to accurately determine an individual's phenotype. To date, no enzyme assay of acid α-glucosidase (GAA) has been described that can differentiate IOPD vs LOPD using blood samples. METHODS We incubated 10 μL leukocyte lysate and 25 μL GAA substrate and internal standard (IS) assay cocktail for 1 h. The reaction was purified by a liquid–liquid extraction. The extracts were evaporated and reconstituted in 200 μL methanol and analyzed by LC-MS/MS for GAA activity. RESULTS A 700-fold higher analytical range was observed with the LC-MS/MS assay compared to the fluorometric method. When GAA-null and GAA-containing fibroblast lysates were mixed, GAA activity could be measured accurately even in the range of 0%–1% of normal. The leukocyte GAA activity in IOPD (n = 4) and LOPD (n = 19) was 0.44–1.75 nmol · h−1 · mg−1 and 2.0–6.5 nmol · h−1 · mg−1, respectively, with no overlap. The GAA activity of pseudodeficiency patients ranged from 3.0–28.1 nmol · h−1 · mg−1, showing substantial but incomplete separation from the LOPD group. CONCLUSIONS This assay allows determination of low residual GAA activity in leukocytes. IOPD, LOPD, and pseudodeficiency patients can be partially differentiated by measuring GAA using blood samples.

scholarly journals Rare Diseases in Neurology — Caring for a Patient with Pompe’s Disease

2019 ◽  
Vol 8 (4) ◽  
pp. 170-176
Author(s):  
Anna Roszmann ◽  
◽  
Mikołaj Hamerski ◽  
Marcelina Skrzypek-Czerko ◽  
◽  
...  
Keyword(s):  
Clinical Picture ◽  
Pompe Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Pompe’S Disease ◽  
Pompe's Disease ◽  
Disease Case ◽  
Nurses Role

Introduction. Pompe disease, a severe metabolic myopathy, is caused by mutations in the gene coding for acid alphaglucosidase (GAA), what lead to intralysosomal accumulation of glycogen in all tissues, most notably in skeletal muscles. Pompe disease was the first documented lysosomal storage disease, nowadays we know around 60 similar disorders. Aim. Presentation of the clinical picture of a man with Pompe’s disease. Case Report. A man at the age of 40, diagnosis of the Pompe’s disease was made only at the age of 31. The first symptoms, indicating the patient’s development of the disease, were already present in the early school age. At first, the clinical picture presented by the patient led to the diagnosis of muscular dystrophy. Discussion. Pompe disease presents as a continuum of clinical phenotypes that differ by age of onset, severity, and organ involvement. Pompe disease affects people of all ages with varying degrees of severity. Two main broad types are recognized based on the onset of symptoms and the presence or absence of cardiomyopathy. Infantile onset Pompe disease (IOPD) as one, and the most severe for mod the disease. Other and less destructive is late-onset Pompe disease (LOPD) manifests any time after 12 months of age. The disease can be successfully treated by enzyme replacement therapy with alglucosidase alfa that was approved for human use in 2006. Conclusions. In big importance is nurses role as educators and support for the patients during their hospitalizations for medicine infusions twice a month. It time when the knowledge and significance of proper life style can be discussed and implemented to empower the patients. (JNNN 2019;8(4):170–176) Key Words: Pompe’s disease, treatment, diagnosis, care

scholarly journals Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

2021 ◽  
Vol 22 (7) ◽  
pp. 3625
Author(s):  
Filomena Napolitano ◽  
Giorgia Bruno ◽  
Chiara Terracciano ◽  
Giuseppina Franzese ◽  
Nicole Piera Palomba ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Rare Variants ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Respiratory Muscles ◽  
Autosomal Recessive Disorder ◽  
Compound Heterozygous ◽  
Enzyme Replacement ◽  
Whole Exome ◽  
Clinical Pictures

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

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 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.

scholarly journals Lessons Learned from Pompe Disease Newborn Screening and Follow-up

2020 ◽  
Vol 6 (1) ◽  
pp. 11
Author(s):  
Tracy L. Klug ◽  
Lori B. Swartz ◽  
Jon Washburn ◽  
Candice Brannen ◽  
Jami L. Kiesling
Keyword(s):  
Newborn Screening ◽  
Pompe Disease ◽  
Human Services ◽  
Lessons Learned ◽  
Lysosomal Storage ◽  
Health And Human Services ◽  
Disease Phenotypes ◽  
Department Of Health ◽  
The World

In 2015, Pompe disease became the first lysosomal storage disorder to be recommended for universal newborn screening by the Secretary of the U.S. Department of Health and Human Services. Newborn screening for Pompe has been implemented in 20 states and several countries across the world. The rates of later-onset disease phenotypes for Pompe and pseudodeficiency alleles are higher than initially anticipated, and these factors must be considered during Pompe disease newborn screening. This report presents an overview of six years of data from the Missouri State Public Health Laboratory for Pompe disease newborn screening and follow-up.

scholarly journals Performance of the Four-Plex Tandem Mass Spectrometry Lysosomal Storage Disease Newborn Screening Test: The Necessity of Adding a 2nd Tier Test for Pompe Disease

2018 ◽  
Vol 4 (4) ◽  
pp. 41 ◽  
Author(s):  
Shu-Chuan Chiang ◽  
Pin-Wen Chen ◽  
Wuh-Liang Hwu ◽  
An-Ju Lee ◽  
Li-Chu Chen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Pompe Disease ◽  
Screening Test ◽  
Disease Screening ◽  
Confirmatory Test ◽  
Tandem Mass ◽  
Lysosomal Storage ◽  
Second Tier

Early diagnosis of lysosomal storage diseases (LSDs) through newborn screening (NBS) has been adapted widely. The National Taiwan University Hospital Newborn Screening Center launched the four-plex tandem mass spectrometry LSD newborn screening test in 2015. The test determined activities of acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), acid β-glucocerebrosidase (ABG; Gaucher), and acid α-l-iduronidase (IDUA; MPS-I) in dried blood spots (DBS). Through 2017, 64,148 newborns were screened for these four LSDs. The screening algorithm includes enzyme activity/ratio as the cutoffs for the first screening test and a second-tier test for Pompe disease screening. The second-tier Pompe disease screening test measured activity inhibition by acarbose. Twenty-nine newborns required a confirmatory test; six were confirmed to have Pompe disease, and nine were confirmed to have Fabry disease. The screen-positive rate for Pompe disease was 0.031%. Therefore, in Pompe disease newborn screening, a validated 2nd tier test is necessary to decrease false positives.

scholarly journals Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

2018 ◽  
Vol 123 (2) ◽  
pp. S21
Author(s):  
Stephanie Austin ◽  
Mugdha Rairikar ◽  
Laura Case ◽  
Lauren Bailey ◽  
Zoheb Kazi ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Pompe Disease ◽  
Late Onset ◽  
The Common ◽  
C 32 ◽  
Insight Into
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