Muscle Weakness and Respiratory Failure From an Orphan Disease: Adult Onset Pompe Disease (Acid Alpha-Glucosidase Deficiency)

CHEST Journal ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 132A ◽  
Author(s):  
Anushya Chelvanathan ◽  
Andrew McIvor ◽  
Nicole Drost
Keyword(s):  
Respiratory Failure ◽  
Muscle Weakness ◽  
Pompe Disease ◽  
Orphan Disease ◽  
Adult Onset ◽  
Alpha Glucosidase

P3.59 Remarkably low acid alpha-glucosidase activity in two patients with adult-onset Pompe disease

2011 ◽  
Vol 21 (9-10) ◽  
pp. 700
Author(s):  
S.C.A. Wens ◽  
J.M. de Vries ◽  
N.A.M. van der Beek ◽  
M. Kroos ◽  
A.J.J. Reuser ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Adult Onset ◽  
Glucosidase Activity ◽  
Alpha Glucosidase

scholarly journals 128 Late-onset pompe disease (LOPD) presenting with fulminant hypercapnic respiratory failure

2019 ◽  
Vol 90 (e7) ◽  
pp. A41.2-A41
Author(s):  
Leon S Edwards ◽  
Michel Tchan ◽  
Kate M Crossley ◽  
Brendon Yee ◽  
Judith M Spies
Keyword(s):  
Respiratory Failure ◽  
Pompe Disease ◽  
Late Onset ◽  
Left Ventricular ◽  
Chronic Respiratory Failure ◽  
Cerebral Stroke ◽  
List Type ◽  
Adult Onset ◽  
Hypercapnic Respiratory Failure ◽  
Initial Symptoms

IntroductionWe report a case of LOPD with acute-on-chronic respiratory failure.CaseA 57 year-old retired farmer presented with obtundation requiring intubation. He reported a 4 month history of hypophonia, intermittent diplopia, lethargy and orthopnea.Initial arterial blood gas measurement displayed acute-on-chronic hypercapnic respiratory failure (pH 7.19, pO2 98 mmHg, pCO2 112 mmHg, HCO3 43 mmol/L). Muscle biopsy was suggestive of LOPD with myofibres demonstrating acid phosphatase and periodic acid-schiff positive vacuoles. Diagnosis was confirmed with low α-glucosidase activity on dried blood spot (0.4umol/h/L) and elevated urinary tetrasaccharide level (5 mmol/mol creatinine). Mutation analysis of the GAA gene demonstrated two known pathogenic mutations (c.-32–13T>G and c.1075+1G>T). With improved ventilation, he was able to be extubated. The only respiratory support on discharge was overnight bilevel positive airway pressure ventilation.ConclusionLOPD is a rare autosomal recessive metabolic disorder caused by a deficiency in acid α-glucosidase. This leads to intra-lysomal accumulation of glycogen in tissues. Particularly in the late form, there is significant phenotypic variability.1 Diagnosis remains challenging. Cases have been reported with a range of initial symptoms including stroke,2 syncope3 and chronic respiratory failure.4 Acute on chronic respiratory failure at presentation is rare.Enzyme replacement therapy has been shown to improve both morbidity and mortality in LOPD.5 Earlier treatment is associated with better outcomes.6 Prompt recognition of cases is paramount. Unexplained acute-on-chronic respiratory failure should raise the possibility of this condition. In such cases, management of ventilation is vital.ReferencesChan J, et al. The emerging phenotype of late-onset Pompe disease: A systematic literature review. Mol Genet Metab 2017;120(3):163–172.Hossain MA, et al. A Case of Adult-onset Pompe Disease with Cerebral Stroke and Left Ventricular Hypertrophy. J Stroke Cerebrovasc Dis 2018;27(11):3046–3052.Walczak-Galezewska M, et al, Late-onset Pompe disease in a 54 year-old sportsman with an episode of syncope: a case report. Eur Rev Med Pharmacol Sci 2017;21(16):3665–3667.O’Callaghan C, et al, Adult-onset Pompe disease presenting with insidious hypercapnic respiratory failure. Respirol Case Rep 2016;4(5):e00178.Schoser B, S A, Kanters S, Hamed A, Jansen J, Chan K, Karamouzian M, Toscano A. Survival and long-term outcomes in late-onset Pompe disease following alglucosidase alfa treatment: a systematic review and meta-analysis. J Neurol 2017;264(4):621–630.Chien YH, HW, Lee NC. Pompe disease: early diagnosis and early treatment make a difference. Pediatr Neonatol 2013;54(4):219–227.

Postoperative acute respiratory failure caused by adult-onset Pompe disease

2016 ◽  
Vol 12 (1) ◽  
pp. 344-346
Author(s):  
Dingyu Tan ◽  
Jun Xu ◽  
Yi Yang ◽  
Ming Gu ◽  
Xuezhong Yu
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Pompe Disease ◽  
Adult Onset

Recombinant human acid alpha-glucosidase (rhGAA) in adult patients with severe respiratory failure due to Pompe disease

2011 ◽  
Vol 21 (7) ◽  
pp. 477-482 ◽  
Author(s):  
David Orlikowski ◽  
Nadine Pellegrini ◽  
Hélène Prigent ◽  
Pascal Laforêt ◽  
Robert Carlier ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Pompe Disease ◽  
Adult Patients ◽  
Severe Respiratory Failure ◽  
Human Acid ◽  
Alpha Glucosidase

Late Onset Pompe Disease with Novel Mutations and Atypical Phenotypes

2021 ◽  
pp. 1-13
Author(s):  
Tanushree Chawla ◽  
Veeramani Preethish-Kumar ◽  
Kiran Polavarapu ◽  
Seena Vengalil ◽  
Mainak Bardhan ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Muscle Weakness ◽  
Pompe Disease ◽  
Late Onset ◽  
Compound Heterozygous ◽  
Muscle Involvement ◽  
Genetic Characteristics ◽  
First Case ◽  
Girdle Muscle ◽  
Gaa Gene

Background: Late onset Pompe disease (LOPD) is rare and generally manifests predominantly as progressive limb girdle muscle weakness. It is linked to the pathogenic mutations in GAA gene, which leads to glycogen accumulation in various tissues. Materials and methods: We describe the unusual clinical, biochemical, histopathological and genetic characteristics of 5 cases of LOPD. Results: The first case had progressive anterior horn cell like disease (AHCD) that evolved later to classical limb girdle syndrome and respiratory failure, the second patient had rigid spine syndrome with gastrointestinal manifestations, the third had limb girdle weakness superimposed with episodic prolonged worsening and respiratory failure, the fourth had large fibre sensory neuropathy without primary muscle involvement and the fifth presented with classical limb girdle muscle weakness. Two homozygous missense mutations c.1461C > A (p.Phe487Leu) and c.1082C > T (p.Pro361Leu) in the GAA gene were identified in case 1 and 2 respectively. Case 3 was compound heterozygous with inframe c.1935_1940del (p.Val646_Cys647del) and an intronic splice effecting variant c.-32-13T > G. Compound heterozygous missense variants c.971C > T (p.Pro324Leu) and c.794G > A (p.Ser265Asn) were identified in case 4. Case 5 had a frameshift insertion c.1396dupG (p.Val466GlyfsTer40) and a synonymous splice affecting variant c.546G > T(p.Thr182=). Conclusion: We are describing for the first time from India on LOPD with unusual phenotypes identified. A high degree of clinical suspicion and diagnosing rare phenotypes of Pompe disease is imperative to consider early initiation of Enzyme Replacement Therapy (ERT).

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.

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