ABSTRACT
A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally.
Subject(s)
Gangliosidoses, GM2/diagnosis , Muscular Atrophy, Spinal/diagnosis , Adult , Diagnosis, Differential , Gangliosidoses, GM2/genetics , Heterozygote , Hexosaminidase A/genetics , Humans , Magnetic Resonance Imaging , Male , MutationABSTRACT
BACKGROUND AND PURPOSE: Diet-induced hypercholesterolaemia exacerbates post-myocardial infarction (MI) ventricular remodelling and heart failure, but the mechanism of this phenomenon remains unknown. This study examined whether worsening of post-MI ventricular remodelling induced by dietary hypercholesterolaemia was related to upregulation of angiotensin II type 1 (AT1) receptor in the rat heart. EXPERIMENTAL APPROACH: MI was induced surgically in rats fed normal or high cholesterol diet. Both groups of rats were then assigned to control, atorvastatin, losartan or atorvastatin+losartan-treated subgroups and followed for 8 weeks. Left ventricular (LV) function was assessed with echocardiography. In isolated hearts, LV pressures were measured with a latex balloon and a tip catheter. AT1-receptor density was assessed in LV membranes with radioligand-binding assays. KEY RESULTS: High cholesterol diet exacerbated LV dilation and dysfunction in post-MI hearts. Atorvastatin or losartan prevented these hypercholesterolaemia-induced effects, whereas their combination was not more effective than each drug alone. AT1 receptors were upregulated 8 weeks after MI, this was further increased by hypercholesterolaemia and restored to baseline levels by atorvastatin. CONCLUSIONS AND IMPLICATIONS: Hypercholesterolaemia exacerbated LV remodelling and dysfunction in post-MI rat hearts and upregulated cardiac AT1 receptors. All these effects were effectively prevented by atorvastatin. Thus, the pleiotropic statin effects may include interference with the renin-angiotensin system through downregulation of AT1 receptors.