Pompe disease presenting as an isolated generalized dilative arteriopathy with repeated brain and kidney infarcts.

Abstract

Pompe disease is a rare metabolic affection caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase encoded by the GAA gene and responsible for the degradation of lysosomal glycogen [1]. Late-onset Pompe disease (LOPD) develops in adults and is usually limited to myopathy [1]. Cardio-cerebrovascular manifestations have been described in addition to myopathy in LOPD, including heart rythm alterations, left ventricular hypertrophy, and cerebral and aortic dilated arteriopathy [2–4]. Here, we describe for the first time a patient with Pompe disease who presented with a pure vascular phenotype of the disease. A 52-year-old male caucasian patient with no past medical or family history presented with an episode of acute left abdominal pain in 2008. Abdominal magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) demonstrated a left kidney infarct, and bilateral dilative renal and iliac arteriopathy without aortic involvement (Fig. 1). Electrocardiography (EKG) and echocardiography were normal, and treatment with aspirin 160 mg/day was introduced. In 2011, he presented with another episode of acute left abdominal pain, and abdominal MRI demonstrated an enlargement of the previously known left kidney infarct. EKG and echocardiography were normal, and aspirin treatment was replaced with an oral anticoagulant, i.e. fluindione. In 2012, the patient presented with an episode of transitory aphasia. Brain MRI revealed an acute ischemic stroke in the territory of the left middle cerebral artery, and neck MRA showed bilateral dilative carotid and vertebral arteriopathy (Fig. 1). EKG and echocardiography were normal, and treatment with fluindione was maintained. Marfan syndrome, Ehlers– Danlos syndrome and Fabry disease were excluded, and Pompe disease was considered despite the patient presenting with no sign of myopathy, i.e. normal motor examination and normal creatine kinase (CK) levels, echocardiography, pulmonary function tests, and muscle biopsy. Muscle biopsy was processed with standard methods for histology, histochemistry, and electron microscopy, including periodic acid-Schiff (PAS) staining. Motor examination included manual muscle testing, timed tests (time to climb 4 steps, to rise from a chair, and to walk 10 m), motor function measurement (MFM scale), and the 6-min walking test. Acid alpha-glucosidase deficiency was found in blood lymphocytes, cultured skin fibroblasts and skeletal muscle, and the patient was a compound heterozygote for 1 previously reported pathogenic variation in intron 1 of the GAA gene (c.-32-13T[G), and 1 newly described pathogenic variation in exon 6 of the GAA gene (p.V350M, c.1048G[A) (Table 1). Two years follow-up showed no additional cerebral or kidney infarcts with oral anticoagulation. As the patient presented with no myopathy, cardiomyopathy and respiratory insufficiency, enzyme replacement therapy was not considered [5]. This is the first description of a patient with Pompe disease presenting with a generalized dilative arteriopathy V. Quenardelle (&) M. Bataillard V. Wolff A. Echaniz-Laguna Departement de Neurologie, Hopitaux Universitaires de Strasbourg, Hopital de Hautepierre, 67098 Strasbourg, France e-mail: veronique.quenardelle@chru-strasbourg.fr