Familial Cholesterolosis with High-Density Lipoprotein Deficiency

The disease has been named after the isle of Tangier off the coast of Virginia where the first cases have been observed. It is characterized by the almost complete absence of high-density lipoproteins and storage of cholesterol and its esters in various tissues. The first observation concerned a five year old boy and his six year old sister. They had no further siblings. Further inquiries revealed that the parents were distantly related. Meanwhile two more affected families have been found in Missouri and Kentucky. The affected families are unrelated (Fredrickson et al. 1962, 1964). 

The available data strongly suggest autosomal recessive inheritance. In the serum of presumed heterozygotes high-density lipoproteins have been shown to be diminished. In homozygous affected individuals this fraction is almost completely lacking, and cholesterol esters are stored in tissues. The plasma cholesterol concentration is diminished, and triglycerides are increased. 

Recent studies demonstrated the presence of an atypical lipoprotein that im-munologically corresponded to the a-lipoprotein, a so-called cross reacting material 

Observation of manifest disease in siblings and consanguinity in at least three of the few known families indicate autosomal recessive inheritance. The parents of one of the patients of Lamy et al. (1963) were halfsibs. This disease, too, seems to be more frequent among Jews. 

Salt et al. (1960) noted in one family a decreased plasma concentration of jS-lipoproteins, cholesterol and phospholipids in assumed heterozygotes (parents and paternal grandfather). These observations have not been confirmed in other families. The possibility to recognize heterozygotes, therefore, remains questionable. 

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