Cryofibrinogenemia, Familial Primary

Clinical Features

Korst and Kratochvil (1955) coined the term cryofibrinogen for a plasma protein that precipitated on cooling and redissolved on rewarming to 37 degrees C. They found the protein associated with lung neoplasm complicated by thrombophlebitis migrans.

Lolin et al. (1989) described a 7-year-old girl who was found to have cryofibrinogenemia after developing transient nephrotic syndrome and hematuria after anesthesia. Heat loss is a common accompaniment of anesthesia because of the use of cold and dry gases, exposure to a cool environment of often vasodilated patients, heat loss from the operation site, the infusion of cold fluids, and abolition of the shivering reflex by muscle relaxants. It is greatest in children because of their larger ratio of surface area to volume. Investigation of the patient's family showed that the trait was familial, probably autosomal dominant inasmuch as male-to-male transmission was observed. An unusual fact was that the cryofibrinogen precipitated at 35 degrees C; usually the temperature necessary to cause precipitation is lower. Both parents of the proband had cryofibrinogenemia. Although not known to be related, both came from Welsh mining valleys. Lolin et al. (1989) raised the possibility of homozygosity in the proband. Several members of the family developed acrocyanosis over uncovered noses and cheeks when exposed to cold for the first time on a skiing holiday in Austria. The mutation in this disorder may involve one of the structural genes for fibrinogen (134820, 134830, 134850).