title: An unusual presentation of Gaucher's disease: aortic valve fibrosis in a patient homozygous for a rare G377S mutation.
abstract: Gaucher's disease (GD) has variable presentations, but cardiac involvement is a generally uncommon clinical manifestation of the disease. In the past 25 years, the underlying genetic disorder in GD has been well characterized, with almost 300 mutations identified in the glucocerebrosidase gene (GBA). Nevertheless, clear genotype-phenotype correlations have been confirmed only for the most frequent mutations. We present a female patient, who was known to have aortic valve pathology from the age of 30. Despite medical follow up, at the age of 60 she presented with heart failure (NYHA III). At that time echocardiography showed severe fibrosed aortic valve stenosis. Valvuloplasty was planned, when thrombocytopenia, previously considered to be autoimmune, became severe. Anemia and leukopenia were also noted. Moderate splenomegaly and severe bone marrow infiltration were found on MRI. Bone marrow aspiration revealed typical Gaucher cells and the enzyme activity assay confirmed the diagnosis. DNA investigation showed that the patient is homozygous for the G377S mutation. To our knowledge, of all mutations identified so far, only homozygosity for the D409H mutation has been associated with cardiovascular valvular disease in patients with a rare type 3c GD. G377S, found in our patient, is a rare mutation, previously reported as a 'mild' mutation, because of the finding that homoallelic patients were essentialy asymptomatic or had mild disease. Our patient, also homozygous for G377S mutation, had a severe form of type 1 GD, with rare cardiac valve involvement, which is a previously unreported clinical presentation for this mutation. This case further proves that patients with the same genotypes can have different phenotypes, emphasizing the influence of other genetic and/or environmental factors.
authors.affiliation: Department of Medicine, Division of Hematology, University Hospital "Merkur", Zagreb, Croatia. zina_peric@yahoo.com
authors.forename: Zinaida
authors.initials: Z
authors.lastname: Perić
authors.forename: Ika
authors.initials: I
authors.lastname: Kardum-Skelin
authors.forename: Biljana Jelić
authors.initials: BJ
authors.lastname: Puskarić
authors.forename: Tomislav
authors.initials: T
authors.lastname: Letilović
authors.forename: Radovan
authors.initials: R
authors.lastname: Vrhovac
authors.forename: Branimir
authors.initials: B
authors.lastname: Jaksić
mesh_terms: D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics; D001706:Biopsy; D004452:Echocardiography; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation
chemical_list: D005962:Glucosylceramidase