LAUSR

Pompe disease or glycogen storage disease type II (GSDII; OMIM #232300) is a rare recessive metabolic disorder caused by a deficiency in the lysosomal acid a-glucosidase activity resulting in lysosomal glycogen accumulation in different tissues. Glycogen accumulation has been detected in skeletal and heart muscles, in smooth muscle of blood vessels, gastrointestinal tract and urinary bladder, leading a multisystemic clinical or subclinical involvement [1]. Enzyme replacement therapy (ERT) changed the natural history of classic form of Pompe disease (infantile onset) and showed to improve or stabilize motor and respiratory performance in 2/3 of LOPD patients [2]. Intracranial artery abnormalities (IAA) in late onset Pompe disease (LOPD) have been described so far in several reports and few systematic studies [3–7]. Previous evidences suggest a potential link between blood vessels anomalies and glycogen storage in smooth muscle cells of the media [1]. The most frequent alterations described are vertebrobasilar dolichoectasia (VTD), internal carotid ectasia (ICE) and aneurysms of middle cerebral artery (AMCA) [6, 7]. Even if the overall prevalence of IAA among Pompe population is estimated around 50% with variable outcome [8–11], the natural course of intracranial vascular anomalies has not been systematically investigated. Between 2006 and 2016, we have systematically monitored the IAA in five out of six previously reported LOPD patients on ERT by magnetic resonance angiography (MRA) performed with the same protocol over the time [6]. One patient required CT scan imaging because of cardiac pacing requirement during the follow-up [12]. Stable radiological follow-up after the first year had been observed [6]. Here, we present the radiological data of the longextended term follow-up of this cohort. The median disease duration was 28.6 years (range 17–39 years) and the median radiological follow-up was 8 years and half (range 7–10 years). At the beginning, three out of five patients (P1, P2, P5) had cerebral arterial anomalies (VBD, ICE, or both) detected by MRA and two (P1, P2) of them had related symptoms (eyelid ptosis due to a neurovascular conflict, transient ischemic attack). The two patients (P3, P4) with normal MRA had the shortest disease duration and milder clinical phenotype. Four patients (P1, P2, P3 and P5) continued ERT therapy without adverse effect all along follow-up duration and one patient (P4) required permanent discontinuation few months later the start of ERT because of major adverse effect. Globally, the MRA findings did not show significant changes between the first and last study in all the patients (Table 1) and none of the patient showed major vascular events (ischemic or hemorrhagic strokes and subarachnoid hemorrhages) during the follow-up. Noteworthy, in our cohort none of the patients had or developed vascular aneurysms. VBD and ICE remained stable (diameter variation\1 mm) in all patients. Novel intracranial arterial abnormalities were not detected in any patients. None of & Matteo Garibaldi [email protected]