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

Abstract

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.