Pompe disease is a lysosomal storage disorder caused by acid-α-glucosidase (GAA) deficiency, leading to glycogen storage. The disease manifests as a fatal cardiomyopathy in infantile form. Enzyme replacement therapy (ERT) has recently prolonged the lifespan of these patients, revealing a new natural history. The neurologic phenotype and the persistence of selective muscular weakness in some patients could be attributed to the central nervous system (CNS) storage uncorrected by ERT. GAA-KO 6neo/6neo mice were treated with a single intrathecal administration of adeno-associated recombinant vector (AAV) mediated gene transfer of human GAA at 1 month and their neurologic, neuromuscular, and cardiac function was assessed for 1 year. We demonstrate a significant functional neurologic correction in treated animals from 4 months onward, a neuromuscular improvement from 9 months onward, and a correction of the hypertrophic cardiomyopathy at 12 months. The regions most affected by the disease i.e. the brainstem, spinal cord, and the left cardiac ventricular wall all show enzymatic, biochemical and histological correction. Muscle glycogen storage is not affected by the treatment, thus suggesting that the restoration of muscle functionality is directly related to the CNS correction. This unprecedented global and long-term CNS and cardiac cure offer new perspectives for the management of patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-017-0464-2) contains supplementary material, which is available to authorized users.

This case report presents a 14-month-old female Poodle mix with acute megakaryoblastic leukemia based on a marked thrombocytosis, abnormal platelet morphology, circulating dwarf megakaryocytes, and blast cells in the blood. Bone marrow abnormalities included dysmegakaryopoiesis dygranulopoiesis, and an increased number of blast cells was observed in the blood. Extensive leukemic involvement was also found in the liver, spleen, lymph nodes, lungs, kidneys, and brain. The cytopathologic features of the abnormal circulating cells were highly suggestive of being megakaryocytic in origin, which was supported by negative myeloperoxidase staining and positive von Willebrand factor staining on immunocytochemistry (ICC). The neoplastic cells were also CD61 positive and had variable von Willebrand factor expression on ICC. Although there were only 25% blast cells in the bone marrow, which theoretically supported myelodysplastic syndrome, the hypothesis that this case represented acute myeloid leukemia of megakaryoblastic origin was confirmed by the continuous increase in circulating blast cell numbers during follow-up visits and the extensive leukemic involvement of parenchymal organs.

Background Brain metastases are well known for disseminated hemangiosarcoma involving the right atrium/auricle. Case report An 8‐year‐old male Australian Shepherd Dog presented with a 3‐day history of circling to the left. A neurological examination revealed obtunded mentation, right hemi‐inattention, bilateral strabismus towards the left side and absent physiological nystagmus. In addition, the dog had muffled heart sounds on auscultation and exercise‐induced weakness. Laboratory findings included hypercoagulability and marked elevation in the C‐reactive protein concentration. Electrocardiography detected a sinus rhythm with right bundle‐branch block and ventricular bigeminy. Echocardiography revealed an extensive interventricular septal mass. Due to the grave prognosis, the owners elected for euthanasia, and a complete necropsy was performed. The main pathological findings were an interventricular septal and left ventricular hemangiosarcoma, with metastases in the brain, lungs, spleen and adrenal glands. No evidence of tumour infiltration was found in the right atrium. Conclusion To the authors' knowledge, this is the first report of neurological signs due to confirmed brain metastases in a dog with interventricular septal hemangiosarcoma. Although the right atrium is the main location for cardiac hemangiosarcoma, the interventricular septum should be evaluated in all cases.

Background Obstructive shock can be caused by any lesion leading to extraluminal compression or intraluminal occlusion of the cardiac chambers or major vessels. Case Report A 12‐year‐old, male castrated, Border Collie cross dog presented to a veterinary teaching hospital for collapse. A physical examination revealed severe vasoconstrictive shock and abdominal distension. Abnormalities on blood tests were consistent with systemic hypoperfusion. Cardiac underfilling, hepatomegaly with distended vasculature and ascites were identified by focused ultrasonography, raising suspicion of obstructive shock. This was supported by the radiographic findings of microcardia and a distended caudal vena cava (CVC). There was transient response to fluid therapy for blood volume expansion. Repeat focused ultrasonography during rapid intravenous fluid administration identified a right intra‐atrial mass, assessed as likely to be causing obstruction of venous return. The dog was humanely euthanased given the guarded prognosis. At postmortem evaluation, a malignant pheochromocytoma in the left adrenal gland with tumour thrombus extending to the tricuspid valve through the CVC was found. The extensive thrombus caused the obstructive shock in this case. Metastasis in a peripheral lymph node and neoplastic emboli in the heart and lungs were also visible at the histopathological evaluation. Conclusion To the best of authors' knowledge, this is the first report of severe obstructive shock secondary to extension of caval tumour thrombus into the right atrium in a dog with malignant pheochromocytoma. Tumour thrombus from a malignant pheochromocytoma should be included as a differential diagnosis of obstructive shock, with or without a visible right intra‐atrial mass, in dogs. Serial focused ultrasonography during intravenous fluid administration can aid diagnosis.