Presentation Of Pompe Disease Research Articles

P.064 A case of late onset Pompe Disease presenting in 6th decade

Background: Late onset Pompe disease (LOPD), rare autosomal recessive lysosomal storage disease, resulting from mutation in alpha glucosidase enzyme (GAA) can present even in 6th decade of life. Slowly progressive, subtle, limb girdle pattern of weakness (LGPW), with auxiliary features such as ptosis, enlarged tongue, axial rigidity, facial diplegia, variable degree of respiratory weakness is not uncommon. Hypertrophic and electrical cardiac abnormalities are well described in LOPD. Methods: We present a case of 67-year-old male presenting with proximal weakness, subtle ptosis, bilateral quadriceps and shoulder girdle atrophy, and left toe numbness. PMHx: CABG, NSTEMI. Statin use. FMHx: noncontributory. Results: EMG: L5 radiculopathy, with unexpected myopathic units in hip/pelvic/ shoulder girdle muscles with active denervation and muscle irritability. CK, CRP, SPEP, ANA, LFTs, HMG-CoA reductase: normal. GAA enzymatic activity=0.96µmol/L/hr (low), genetics: pathogenic variants in GAA gene: c.-32-13T>G and c.1194+3G>C. ECHO: severe diastolic dysfunction, restrictive left ventricular filling. PFTs: normal. Diagnosed with LOPD, started on therapy. Conclusions: LOPD remains a differential for LGPW especially in older patient population with history of cardiopulmonary features. Age-appropriate conconminant pathologies may confound the diagnostic process.Symptoms may preceed diagnosis for years.GAA enzymatic activity followed by genetic testing remains readily available and can confirm diagnosis, preventing delay of approved therapy.

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

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.

Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease

Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle disease-genes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T >G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results.

Perioperative management of children with glycogen storage disease type II-Pompe disease.

Pompe disease is a rare metabolic disorder caused by a deficiency of the lysosomal enzyme acid α-glucosidase. Glycogen accumulation damages skeletal, cardiac, and smooth muscles, causing a progressive and debilitating muscle weakness and cardiomyopathy. As life expectancy has much improved since the introduction of enzyme replacement therapy an increasing number of patients are referred for surgical procedures. Due to the potential cardiopulmonary complications, these patients form a high-risk group for the anesthesiologist. In this study, we investigated the incidence of perioperative complications in children with Pompe disease treated in our hospital since the introduction of enzyme replacement therapy. Anesthetic and perioperative data of children with Pompe disease treated between 1999 and 2015 in the Erasmus MC-Sophia Children's Hospital, University Medical Centre, Rotterdam, The Netherlands, were collected, retrospectively. Of the 65 children with Pompe disease, 34 patients underwent in total 77, mostly low-risk, surgical procedures. Twenty-one children had the classic infantile form and 13 had a nonclassic presentation of Pompe disease. In 13 (16.8%) procedures, 1 or more perioperative complications occurred. Perioperative desaturation was the main complication (12.9%), followed by arrhythmia (3.8%) and heart failure requiring diuretic treatment (2.6%). One child died 2days postoperatively, but this was considered unrelated to the procedure. Despite the potentially high anesthetic risk for children with Pompe disease under enzyme replacement therapy, the incidence of perioperative complications in our study was relatively low. Our data suggest that with proper precautionary measures and a critical choice of timing of the operation, general anesthesia in children with Pompe disease could be relatively safe nowadays.

Isolated Triceps Myositis as an Initial Presentation of Pompe Disease (P5.060)

Isolated Triceps Myositis as an Initial Presentation of Pompe Disease (P5.060)

Novel presentation of Pompe disease: Inclusion‐body myositis‐like clinical phenotype

Novel presentation of Pompe disease: Inclusion‐body myositis‐like clinical phenotype

A Case of Late-Onset Pompe Disease Occurring with a Muscle Weakness Pattern Similar to that of Facioscapulohumeral Muscular Dystrophy

Pompe or glycogen storage disease type II is an autosomal recessive disorder, caused by an accumulation of glycogen in the lysosome. The clinical spectrum ranges from the classic form with early onset and severe phenotype to the non-classic form with later onset and different phenotype. In fact, the clinical presentation of Pompe disease can resemble that of many musculoskeletal disorders. According to the clinical variability of the disease, we report a 48-yearold man with the adult form of acid maltase defi ciency showing many clinical similarities to facioscapulohumeral muscular dystrophy (FSHD).

Highlighting intrafamilial clinical heterogeneity in late-onset Pompe disease

Background/aimsPompe disease is a rare metabolic disorder caused by deficiency of the lysosomal enzyme acid alpha-glycosidase (GAA). The late onset form of the disease is characterized by muscle weakness and respiratory involvement of variable severity. The aim of this short communication is to highlight the clinical variability of Pompe disease within siblings suffering from the disease. Case reportsWe report three pairs of siblings with late-onset Pompe disease presenting with different clinical phenotypes within the spectrum of disease phenotypes. ConclusionClinical manifestations in Pompe disease within the same family can be very different. Clinicians should investigate patients' siblings for symptoms throughout the entire spectrum of the disease in order to avoid delays in the diagnosis and to pick-up mildly affected persons as early as possible, when they can benefit the most from enzyme replacement therapy.

Adult-Onset Pompe Disease Presenting with Severe Fatigue and Selective Involvement of Type 1 Muscle Fibers

Limb-girdle weakness is the most common and prominent presenting sign in adults with Pompe disease. Light-microscopic examination of skeletal muscle from Pompe disease patients usually reveals a vacuolar myopathy and glycogen storage with nonselective involvement of the different muscle fiber types.

A case of adult Pompe disease presenting with severe fatigue and selective involvement of type 1 muscle fibers

We present a case of adult Pompe disease (acid maltase deficiency) with an uncommon clinical presentation characterized by severe fatigue and myalgia prior to the onset of limb girdle weakness. Remarkably, the muscle biopsy demonstrated selective involvement of type 1 muscle fibers. The cause and clinical effects of fiber type specific involvement are currently unknown, but the phenomenon might contribute to the clinical heterogeneity in Pompe disease and the variable response to enzyme replacement therapy.

19. An unusual case of Pompe disease presenting as muscular dystrophy

19. An unusual case of Pompe disease presenting as muscular dystrophy

Pompe's disease presenting as hypertrophic myocardiopathy with Wolff-Parkinson-White syndrome

Pompe's disease presenting as hypertrophic myocardiopathy with Wolff-Parkinson-White syndrome