EP 42. Smooth muscle involvement in Glycogenosis Type II: Thalamus hemorrhage, increased blood flow and dolichoectasia in a late-onset Pompe patient

Abstract

Pompe disease (Glycogenosis Type II) is a rare autosomal-recessive disorder caused by mutations in the GAA gene encoding for the lysosomal α-glucosidase (acid maltase, GAA). The reduced enzyme activity results in glycogen accumulation in several tissues, particularly skeletal and cardiac muscles, leading to muscular weakness, respiratory and cardiac insufficiency. Enzyme replacement therapy (ERT) has been shown to delay ventilator dependence and a prolong survival. However, in Pompe disease also smooth muscles are affected, but only little is known about the influence of glycogen accumulation in cerebral arteries and its impact on the cerebral blood flow and the progression of dolichoectasia. We report about a 75 years old woman with a known diagnosis of late-onset Pompe disease (GAA mutation IVS1-13T>G, c.2481+102_2646+31del) who presented with a sudden onset of dysarthria and right hemiparesis. The magnetic resonance imaging (MRI) revealed a hemorrhage in the left thalamus and a remarkable vertebrobasilar dolichoectasia. Enzyme replacement therapy with algucosidase alfa (Myozyme®) had been applicated since 8 years (biweekly infusions of 40 mg/kg body weight) under which the patient had experienced a slowly progressive muscular weakness with decreasing mobility. However she had been able to walk with assistance and had no ventilatory support. Data of the cerebral artery status in this patient had been obtained by MR-angiography and duplexsonography four years before as baseline data and as follow up to the current timepoint, allowing the investigation of possible vascular manifestations of Pompe disease. Compared to the baseline data (Hensel et al., 2015) the diameters of the basilar artery (BA) and the posterior cerebral artery (PCA) had expanded during the observation time of 4 years: BA from 5.7 mm to 7 mm; PCA left from 2.1 mm to 2.5 and right 2.1 to 2.5 mm; all arteries measured 1 cm after origin. Diameters of the middle cerebral artery, anterior cerebral artery, the internal carotid artery and the intracerebral vertebral artery (VA) at the V4 segment remained nearly unchanged. Duplexsonography confirmed dilated VA at the V2-segment and increased blood flow: baseline: left 286 ml/min, right 126 ml/min; follow up: left 128 ± 19 ml/min, right 214 ± 41 ml/min; normal range 60 ± 30 ml/min. The blood flow in the extracranial ICA was slightly elevated but still in the normal range: baseline: left 249 ml/min, right 405 ml/min; follow up: left 537 ± 125 ml/min, right 427 ± 36 ml/min; normal range: 311 ± 119 ml/min. This case report stresses the systemic character of Pompe disease and underlines the importance of screening for symptoms other than skeletal muscle weakness. Intracerebral hemorrhage occurred in a patient with a prominent increase in blood flow and dolichoectasia of vertebrobasilar arteries in the baseline study (Hensel et al., 2015) and in the follow up analysis, despite the regular application of ERT. This supports the hypothesis, that ERT does not cross the blood-brain barrier. The risk of ICH due to dolichoectasia and wall sheer stress is an important outcome factor in the face of a prolonged survival of Pompe patients under ERT.