scholarly journals Diagnostic Yield of Chilaiditi’s Sign in Advanced-Phase Late-Onset Pompe Disease

2021 ◽  
Author(s):  
Junichiro Takahashi ◽  
Madoka Mori-Yoshimura ◽  
Hajime Ariga ◽  
Noriko Sato ◽  
Ichizo Nishino ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset ◽  
Diagnostic Yield ◽  
Abdominal Ct ◽  
Glycogen Accumulation ◽  
Abnormal Position ◽  
Liver Atrophy ◽  
Clinical Variables ◽  
Advanced Phase ◽  
Chilaiditi’S Sign

Abstract Purpose: Chilaiditi’s sign (CS), hepatodiaphragmatic interposition of the intestine, was caused by morphological abnormalities such as diaphragmatic atrophy, intestinal dilation, and liver atrophy. The sign is potentially important due to associations with clinically recurrent abdominal pain or even colonic volvulus. In general, neuromuscular disease (NMD) could have the high prevalence of CS because of widened hepatodiaphragmatic space, following diaphragmatic atrophy. Particularly, in late-onset Pompe disease (LOPD), glycogen accumulation in smooth muscle of intestine could lead to the abnormal dilation of intestine. Though the prevalence of CS in LOPD could be high because of developing two main factors of CS, no studies have evaluated the prevalence of CS in LOPD. Our aim was to investigate the prevalence of CS in LOPD, and to identify the risk factors of CS in LOPD patients. Methods: Medical records of genetically confirmed patients of Pompe disease at the National Center Hospital, National Center of Neurology and Psychiatry were retrospectively reviewed. We evaluated CS using chest X-ray (CXR) and abdominal CT and assessed the prevalence of CS in LOPD patients. We also divided the patients into two groups, CS and non-CS group, and evaluated the factor associated with CS compared to clinical variables between groups. Results: Three of seven (43%) were detected in CS. CS group (P5-7) and non-CS group (P1-4) were obtained. In comparison of clinical variables, the severity of atrophy in right diaphragms was significantly higher in CS than non-CS groups (p =0.029). Also, the frequency of abnormal position of right diaphragm and liver, and abnormally dilated bowel was seen in all of CS patients, but none of non-CS patient (p = 0.029, each). Conclusion: In LOPD patients, the prevalence of CS was much higher of 43%, compared to healthy groups, or even in similarly respiratory muscle impaired neuromuscular diseases such as Duchenne muscular dystrophy (DMD) or Myotonic dystrophy type 1 (DM1). The anatomically abnormal position of diaphragm and liver, atrophy and fat infiltration of diaphragms, and abnormally dilated bowel were significantly associated with CS in LOPD. Since CS can cause intestinal symptoms or even contribute to sudden-death of intestinal volvulus, we should pay more attention to CXR or abdominal CT as follow up in LOPD patients.

scholarly journals Late-Onset Pompe Disease with Nemaline Bodies

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
E. Frezza ◽  
C. Terracciano ◽  
M. Giacanelli ◽  
E. Rastelli ◽  
G. Greco ◽  
...  
Keyword(s):  
Muscle Biopsy ◽  
Pompe Disease ◽  
Late Onset ◽  
Molecular Genetic ◽  
Histological Finding ◽  
Autosomal Recessive Disorder ◽  
Glycogen Accumulation ◽  
Muscle Disorders ◽  
Alpha Glucosidase ◽  
Nemaline Bodies

Pompe disease is an autosomal recessive disorder characterized by deficiency of alpha-glucosidase, a lysosomal enzyme, which can lead to glycogen accumulation in skeletal muscle, heart, and nervous system. Clinical presentation is highly variable, with infantile and late-onset (LOPED) forms. Although muscle biopsy findings are rather stereotyped, atypical features have been described. A 52-year-old man without a family history of muscle disorders presented with slowly progressing upper and lower limb girdle weakness and hyperCKemia. At needle EMG, a diffuse neurogenic pattern was detected. Muscle biopsy showed a selective type 1 fiber atrophy with vacuoles of various sizes, filled with PAS and acid phosphatase positive material, confirmed to be glycogen by electron microscopy (EM). Many atrophic fibers contained foci of myofibrillar material recognized as nemaline bodies (NBs) at EM. Low level of alpha-glucosidase activity in blood and molecular genetic testing confirmed the diagnosis of late-onset Pompe disease (LOPED). Major causes of hereditary and acquired NB myopathy were ruled out. In conclusion, NBs represent a novel histological finding in LOPED and characterize the atypical presentation of our case.

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.

Late onset Pompe Disease in India – Beyond the Caucasian phenotype

2021 ◽  
Author(s):  
Ratna Dua Puri ◽  
Nitika Setia ◽  
Vinu N ◽  
Sujatha Jagadeesh ◽  
Sheela Nampoothiri ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset

NEO1/NEO-EXT studies: Safety and exploratory efficacy of repeat avalglucosidase alfa dosing after up to 6 years in participants with late-onset pompe disease (LOPD)

2021 ◽  
Vol 132 (2) ◽  
pp. S34
Author(s):  
Mazen M. Dimachkie ◽  
Richard J. Barohn ◽  
Barry Byrne ◽  
Ozlem Goker-Alpan ◽  
Priya S. Kishnani ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Late Onset

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 Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 8
Author(s):  
Yu-Shan Cheng ◽  
Shu Yang ◽  
Junjie Hong ◽  
Rong Li ◽  
Jeanette Beers ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pompe Disease ◽  
Drug Efficacy ◽  
Cns Involvement ◽  
Glycogen Accumulation ◽  
Induced Pluripotent ◽  
Alpha Glucosidase

Pompe disease is a lysosomal storage disorder caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene. Acid alpha-glucosidase deficiency leads to abnormal glycogen accumulation in patient cells. Given the increasing evidence of central nervous system (CNS) involvement in classic infantile Pompe disease, we used neural stem cells, differentiated from patient induced pluripotent stem cells, to model the neuronal phenotype of Pompe disease. These Pompe neural stem cells exhibited disease-related phenotypes including glycogen accumulation, increased lysosomal staining, and secondary lipid buildup. These morphological phenotypes in patient neural stem cells provided a tool for drug efficacy evaluation. Two potential therapeutic agents, hydroxypropyl-β-cyclodextrin and δ-tocopherol, were tested along with recombinant human acid alpha-glucosidase (rhGAA) in this cell-based Pompe model. Treatment with rhGAA reduced LysoTracker staining in Pompe neural stem cells, indicating reduced lysosome size. Additionally, treatment of diseased neural stem cells with the combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol significantly reduced the disease phenotypes. These results demonstrated patient-derived Pompe neural stem cells could be used as a model to study disease pathogenesis, to evaluate drug efficacy, and to screen compounds for drug discovery in the context of correcting CNS defects.

Expanding the phenotype of late-onset pompe disease: Tongue weakness: A new clinical observation

2011 ◽  
Vol 44 (6) ◽  
pp. 897-901 ◽  
Author(s):  
Alberto Dubrovsky ◽  
Jose Corderi ◽  
Min Lin ◽  
Priya S. Kishnani ◽  
Harrison N. Jones
Keyword(s):  
Pompe Disease ◽  
Clinical Observation ◽  
Late Onset
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