Unusual expression of Gaucher's disease: cardiovascular calcifications in three sibs homozygous for the D409H mutation.
Three sisters suffering from an unusual form of Gaucher's disease are described. These patients had cardiovascular abnormalities consisting of calcification of the ascending aorta and of the aortic and mitral valves. Neurological findings included ophthalmoplegia and saccadic eye movements in two patients, and tonic-clonic seizures in the third. The three patients died, two of them after having undergone aortic valve replacement. Tissue was obtained from one of the sibs and fibroblast and liver beta-glucocerebrosidase activity was reduced to 4% and 11% of mean normal values. Genotype analysis indicated that the patient was homozygous for the D409H mutation. It is tempting to relate the phenotype of severe cardiac involvement to the D409H/D409H genotype, although further cases will be needed before this association can be confirmed.
Institut de Bioquímica Clínica, Corporació Sanitaria, Cerdanyola del Vallès, Barcelona, Spain.
A
A
Chabás
B
B
Cormand
D
D
Grinberg
J M
JM
Burguera
S
S
Balcells
J L
JL
Merino
I
I
Mate
J A
JA
Sobrino
R
R
Gonzàlez-Duarte
L
L
Vilageliu
D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005776:Gaucher Disease / Q000235:genetics* / Q000473:pathology; D005962:Glucosylceramidase / Q000172:deficiency; D006720:Homozygote; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational
D005962:Glucosylceramidase