Severe valvular and aortic arch calcification in a patient with Gaucher's disease homozygous for the D409H mutation.
Gaucher's disease is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase, which leads to glucocerebroside accumulation in the reticuloendothelial system. Homozygosity for the D409H mutation has been associated with cardiovascular valvular disease. We present a case of a 17-year-old Palestinian patient who presented with severe aortic and mitral valvular calcification, as well as calcification of the ascending aorta, the aortic arch and the ostia of his coronary arteries. The patient was confirmed to be homozygous for the D409H mutation in the glucocerebrosidase gene. The patient's enzyme assay for glucocerebrosidase activity was 5 nm/h/mg protein (normal 13-22 nm/h/mg). The patient presented with symptoms of dyspnea and chest pain. He had a 6-year history of documented aortic valve calcification by echocardiogram after two of his older brothers died of congestive heart failure and severe valvular calcification. Cardiac catheterization showed a severely calcified aorta with almost no motion of the aortic valve leaflets and severe calcification of the mitral valve and the mitral valvular apparatus. The patient underwent extensive cardiac surgery with aortic and mitral valve replacements and intraoperative findings confirmed calcification of the entire aortic root. Electron microscopy of the valves confirmed the presence of Gaucher's cells. Enzyme therapy with imiglucerase was initiated. The patient is in stable condition, 20 months post-operatively.
George
R
R
Department of Hematology/Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA. georger@ccf.org
McMahon
J
J
Lytle
B
B
Clark
B
B
Lichtin
A
A
D000293:Adolescent; D019943:Amino Acid Substitution; D001013:Aorta, Thoracic / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D005776:Gaucher Disease / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008943:Mitral Valve / Q000473:pathology* / Q000648:ultrastructure; D009154:Mutation