scholarly journals Importance of Timely Treatment Initiation in Infantile-Onset Pompe Disease, a Single-Centre Experience

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1026
Author(s):  
Javier de las Heras ◽  
Ainara Cano ◽  
Ana Vinuesa ◽  
Marta Montes ◽  
María Unceta Suarez ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Early Treatment ◽  
Pompe Disease ◽  
Treatment Initiation ◽  
Specific Treatment ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Single Centre Experience ◽  
Alglucosidase Alfa ◽  
Infantile Pompe Disease

Classic infantile Pompe disease (IPD) is a rare lysosomal storage disorder characterized by severe hypertrophic cardiomyopathy and profound muscle weakness. Without treatment, death occurs within the first 2 years of life. Although enzyme replacement therapy (ERT) with alglucosidase alfa has improved survival, treatment outcome is not good in many cases and is largely dependent on age at initiation. The objective of the study was (a) to analyse the different stages in the diagnosis and specific treatment initiation procedure in IPD patients, and (b) to compare clinical and biochemical outcomes depending on age at ERT initiation (<1 month of age vs. <3 months of age). Here, we show satisfactory clinical and biochemical outcomes in two IPD patients after early treatment initiation before 3 months of life with immunomodulatory therapy in the ERT-naïve setting, with a high ERT dose from the beginning. Despite the overall good evolution, the patient who initiated treatment <1 month of life presented even better outcomes than the patient who started treatment <3 months of life, with an earlier normalization of hypertrophic cardiomyopathy, along with CK normalization, highlighting the importance of early treatment initiation in this progressive disease before irreversible muscle damage has occurred.

scholarly journals Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1339
Author(s):  
Naresh K. Meena ◽  
Nina Raben
Keyword(s):  
Pompe Disease ◽  
Specific Treatment ◽  
Lysosomal Storage Diseases ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Monogenic Diseases ◽  
Progressive Accumulation ◽  
Alpha Glucosidase

Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The discovery that acid alpha-glucosidase resides in the lysosome gave rise to the concept of lysosomal storage diseases, and Pompe disease became the first among many monogenic diseases caused by loss of lysosomal enzyme activities. The only disease-specific treatment available for Pompe disease patients is enzyme replacement therapy (ERT) which aims to halt the natural course of the illness. Both the success and limitations of ERT provided novel insights in the pathophysiology of the disease and motivated the scientific community to develop the next generation of therapies that have already progressed to the clinic.

scholarly journals Moss-Derived Human Recombinant GAA Provides an Optimized Enzyme Uptake in Differentiated Human Muscle Cells of Pompe Disease

2020 ◽  
Vol 21 (7) ◽  
pp. 2642 ◽  
Author(s):  
Stefan Hintze ◽  
Sarah Limmer ◽  
Paulina Dabrowska-Schlepp ◽  
Birgit Berg ◽  
Nicola Krieghoff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Replacement Therapy ◽  
Pompe Disease ◽  
Muscle Cells ◽  
Lysosomal Storage ◽  
Glycosylation Pattern ◽  
Enzyme Replacement ◽  
Alglucosidase Alfa ◽  
Alternative Drug ◽  
Lysosomal Accumulation

Pompe disease is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of lysosomal acid alpha-glucosidase (GAA). The result of the GAA deficiency is a ubiquitous lysosomal and non-lysosomal accumulation of glycogen. The most affected tissues are heart, skeletal muscle, liver, and the nervous system. Replacement therapy with the currently approved enzyme relies on M6P-mediated endocytosis. However, therapeutic outcomes still leave room for improvement, especially with regard to skeletal muscles. We tested the uptake, activity, and effect on glucose metabolism of a non-phosphorylated recombinant human GAA produced in moss (moss-GAA). Three variants of moss-GAA differing in glycosylation pattern have been analyzed: two with terminal mannose residues in a paucimannosidic (Man3) or high-mannose (Man 5) configuration and one with terminal N-acetylglucosamine residues (GnGn). Compared to alglucosidase alfa the moss-GAA GnGn variant showed increased uptake in differentiated myotubes. Moreover, incubation of immortalized muscle cells of Gaa−/− mice with moss-GAA GnGn led to similarly efficient clearance of accumulated glycogen as with alglucosidase alfa. These initial data suggest that M6P-residues might not always be necessary for the cellular uptake in enzyme replacement therapy (ERT) and indicate the potential of moss-GAA GnGn as novel alternative drug for targeting skeletal muscle in Pompe patients.

Resolution of severe cardiomyopathy in infantile Pompe disease

2013 ◽  
Vol 25 (1) ◽  
pp. 146-148
Author(s):  
John J. Parent ◽  
Marcus Schamberger
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Pompe Disease ◽  
Inborn Error ◽  
Inborn Error Of Metabolism ◽  
Enzyme Replacement ◽  
Infantile Pompe Disease ◽  
Rare Inborn Error

AbstractInfantile Pompe disease is a rare inborn error of metabolism characterized by severe hypertrophic cardiomyopathy and generalised hypotonia occurring in infancy. We present a case of an infant with severe hypertrophic cardiomyopathy that resolved after treatment with enzyme replacement therapy.

scholarly journals Infantile Pompe disease treatment with Myozyme in Chaharmahal and Bakhtiari: A case report

2019 ◽  
Vol 21 (3) ◽  
pp. 149-152
Author(s):  
Nabiollah Asadpour ◽  
Najmeh Bagheri-Kakolaki
Keyword(s):  
Case Report ◽  
Respiratory Distress ◽  
Pompe Disease ◽  
Systolic Dysfunction ◽  
Failure To Thrive ◽  
Glycogen Storage ◽  
Lysosomal Storage ◽  
Feeding Difficulties ◽  
Enzyme Replacement ◽  
Infantile Pompe Disease

Pompe disease is a lysosomal storage disorder that results from an inborn error of metabolism which involves abnormal glycogen storage. Infantile-onset Pompe disease is the most severe phenotype that manifests with the findings of hypotonia, generalized muscle weakness, feeding difficulties, a failure to thrive, hearing loss, hypertrophic cardiomyopathy with systolic dysfunction, and respiratory distress. There is no effective treatment for Pompe disease and clinical control includes primary support health care. However, recent studies have reported that enzyme replacement therapy (ERT) can effectively decrease the symptoms or severity of the disease. The present study is a case report of a 24-day patient with infantile-onset Pompe disease who presented coughing and respiratory distress. The infant experienced fatigue during breastfeeding from the birth and developed dry and nonproductive coughs and perioral cyanosis from two weeks after the birth. The echocardiogram demonstrated left and right ventricular enlargement, mitral and tricuspid regurgitation, and pulmonary hypertension. After definitive diagnosis, the patient was administered with 20 mg/kg of alglucosidase 50 mg vial once every two weeks. He experienced significant improvement in body weight and echocardiogram and symptoms such as fatigue during breastfeeding and perioral cyanosis disappeared completely while he was under Myozyme treatment. In general, the observations confirmed the efficacy of Myozyme in a patient with infantile Pompe disease. Therefore, early diagnosis and quick treatment of Pompe disease with Myozyme can lead to acceptable outcomes, improve conditions, and finally, increase the chance of survival in these patients.

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