Resistance to activated protein C and Legg-Perthes disease.
Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.
Glueck
C J
CJ
Cholesterol Center, Jewish Hospital.
Brandt
G
G
Gruppo
R
R
Crawford
A
A
Roy
D
D
Tracy
T
T
Stroop
D
D
Wang
P
P
Becker
A
A
D001778:Blood Coagulation Disorders / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D001780:Blood Coagulation Tests; D002648:Child; D005165:Factor V / Q000032:analysis; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007873:Legg-Calve-Perthes Disease / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011486:Protein C / Q000378:metabolism*
D011486:Protein C; C095381:factor V Leiden; D005165:Factor V