scholarly journals New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside

2021 ◽  
Vol 10 (15) ◽  
pp. 3395
Author(s):  
Aditi Korlimarla ◽  
Jeong-A Lim ◽  
Paul McIntosh ◽  
Kanecia Zimmerman ◽  
Baodong D. Sun ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Disease Burden ◽  
Late Onset ◽  
Smooth Muscles ◽  
Lessons Learned ◽  
Muscle Pathology ◽  
Gi Tract ◽  
Glycogen Accumulation ◽  
Enzyme Replacement ◽  
Patient Reported

Background: There are new emerging phenotypes in Pompe disease, and studies on smooth muscle pathology are limited. Gastrointestinal (GI) manifestations are poorly understood and underreported in Pompe disease. Methods: To understand the extent and the effects of enzyme replacement therapy (ERT; alglucosidase alfa) in Pompe disease, we studied the histopathology (entire GI tract) in Pompe mice (GAAKO 6neo/6neo). To determine the disease burden in patients with late-onset Pompe disease (LOPD), we used Patient-Reported Outcomes Measurements Information System (PROMIS)-GI symptom scales and a GI-focused medical history. Results: Pompe mice showed early, extensive, and progressive glycogen accumulation throughout the GI tract. Long-term ERT (6 months) was more effective to clear the glycogen accumulation than short-term ERT (5 weeks). GI manifestations were highly prevalent and severe, presented early in life, and were not fully amenable to ERT in patients with LOPD (n = 58; age range: 18–79 years, median age: 51.55 years; 35 females; 53 on ERT). Conclusion: GI manifestations cause a significant disease burden on adults with LOPD, and should be evaluated during routine clinical visits, using quantitative tools (PROMIS-GI measures). The study also highlights the need for next generation therapies for Pompe disease that target the smooth muscles.

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 Acute respiratory failure as presentation of late-onset Pompe disease complicating the diagnostic process as a labyrinth: a case report

2018 ◽  
Vol 13 ◽  
Author(s):  
Francesco Menzella ◽  
Luca Codeluppi ◽  
Mirco Lusuardi ◽  
Carla Galeone ◽  
Franco Valzania ◽  
...  
Keyword(s):  
Case Report ◽  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Pompe Disease ◽  
Late Onset ◽  
Correct Diagnosis ◽  
Ventilatory Support ◽  
Diagnostic Process ◽  
Caucasian Woman ◽  
Enzyme Replacement

Background: Acute respiratory failure can be triggered by several causes, either of pulmonary or extra-pulmonary origin. Pompe disease, or type II glycogen storage disease, is a serious and often fatal disorder, due to a pathological accumulation of glycogen caused by a defective activiy of acid α-glucosidase (acid maltase), a lysosomal enzyme involved in glycogen degradation. The prevalence of the disease is estimated between 1 in 40,000 to 1 in 300,000 subjects. Case presentation: This case report describes a difficult diagnosis of late-onset Pompe disease (LOPD) in a 52 year old Caucasian woman with acute respiratory failure requiring orotracheal intubation and subsequent tracheostomy for long-term mechanical ventilation 24 h/day. Despite a complex diagnostic process including several blood tests, bronchoscopy with BAL, chest CT, brain NMR, electromyographies, only a muscle biopsy allowed to reach the correct diagnosis. Discussion: The most frequent presentation of myopathies, including LOPD, is proximal limb muscle weakness. Respiratory related symptoms (dyspnea on effort, reduced physical capacity, recurrent infections, etc.) and respiratory failure are often evident in the later stages of the diseases, but they have been rarely described as the onset symptoms in LOPD. In our case, a third stage LOPD, the cooperation between pulmonologists and neurologists was crucial in reaching a correct diagnosis despite a very complex clinical scenario due to different confounding co-morbidities as potential causes of respiratory failure and an atypical presentation. In this patient, enzyme replacement therapy with infusion of alglucosidase alfa was associated with progressive reduction of ventilatory support to night hours, and recovery of autonomous walking.

Pompe Disease

2016 ◽  
Author(s):  
Ans T. van der Ploeg ◽  
Pascal Laforêt
Keyword(s):  
Pompe Disease ◽  
Late Onset ◽  
Data Gathering ◽  
Autosomal Recessive Disorder ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Walking Distance ◽  
Patient Registries ◽  
Enzyme Replacement ◽  
Progressive Muscle Weakness

Pompe disease, also named acid maltase deficiency and glycogen storage disease type II (GSDII), is a rare autosomal recessive disorder caused by the deficiency of the glycogen-degrading lysosomal enzyme acid α‎-glucosidase. The clinical spectrum of this disease is broad, varying from a lethal infantile-onset generalized myopathy including cardiomyopathy, to late-onset slowly progressive muscle weakness mimicking limb-girdle muscular dystrophy. Respiratory insufficiency is a frequent complication and the main cause of death. The prognosis of Pompe disease has changed considerably with the use of enzyme replacement therapy using recombinant acid α‎-glucosidase (alglucosidase alfa), which has been widely available since 2006. Improvements in survival and major motor achievements can be observed in patients with infantile forms, and recent studies demonstrate improvement of walking distance and stabilization of pulmonary function in late-onset forms. A longer-term study of the safety and efficacy of ERT, based on data gathering across the complete spectrum of Pompe disease via national or international patient registries, is needed in order to formulate more precise guidelines for treatment.

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