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Primary hyperbetalipoproteinemia (type II hyperlipoproteinemia) is a common disorder associated with premature vascular disease. It is frequently due to genetic abnormalities, some of which are expressed in childhood. We have examined the manner in which that form of hyperbetalipoproteinemia known as familial hypercholesterolemia may be expressed in 236 children aged 1-19 born of 90 matings in which one parent had hyperbetalipoproteinemia of this variety and one parent did not.Two Gaussian populations were fitted to the distribution of both low density lipoprotein cholesterol (C(LDL)) and plasma cholesterol (C) in these children and a likelihood ratio test strongly favored a two over a one population model for both C(LDL) (X(2) = 18.41, P < 0.0005) and C (X(2) = 7.81, P < 0.025). 45% of the children were in the population identified as affected; their mean C(LDL) was 229. The remaining 55% were in the normal population with a mean C(LDL) of 110 which was indistinguishable from that of an unrelated control population, aged 1-19. On the basis of an assumed frequency of hyperbetalipoproteinemia in the general population of 5%, the Edwards' test indicated that a polygenic model of inheritance was highly unlikely (expected, 22%; observed, 45%). The segregation ratio obtained from the derived intersection between the two population curves (C(LDL), 164 mg/100 ml; C, 235 mg/100 ml) was 45/55 (abnormal/normal). The percentage of abnormal children in the first decade (52%) significantly exceeded that in the second (39%) (P < 0.01). The ratios (II/N) were 50/47 and 55/84 in the offspring of affected female and male parents, respectively (X(2) = 3.819, 0.05 < P < 0.10). Only 10% of hyperbetalipoproteinemic children were considered to have hyperglyceridemia. These children, frequently, but not invariably, had a parent with hyperglyceridemia in addition to hyperbetalipoproteinemia (P < 0.05). None of the affected children who were examined had ischemic heart disease (IHD) and 7% had tendon xanthomas. Half of the parents (mean age, 37.4 yr) who were examined had IHD and three-quarters had xanthomas. The data agree well with the hypothesis that hyperbetalipoproteinemia is inherited as a monogenic trait with early expression in these children. More than one genetic defect within the group is not excluded, but retrospective analyses of the 345 first-degree adult relatives of the affected parents indicated that most of the abnormal parents probably represented familial hypercholesterolemia, rather than combined hyperlipidemia, the other most generally recognized form of familial hyperbetalipoproteinemia.

The relation between xanthomatosis and plasma lipid and lipoprotein concentrations has been studied in 336 subjects (172 males and 164 females) with xanthomatosis. With a few exceptions, these patients were either born or lived in Ostfold county, which has a population of about 220 000. Xanthomas had made their first appearance in half the subjects by the age of 48 years. The most frequent localizations of xanthomas were the extensor finger and the Achilles tendons, the former site being more common in males and the latter in females. Tuberotendinous xanthomas were found in 7% of the cases, whereas only one subject had tuberous xanthomas without tendinous involvement. Xanthelasmas were found in 1/3 of the females and 1/6 of the males. The size of xanthomas and the number of xanthoma sites increased with age and cholesterol levels. Cholesterol concentrations were (or had been) increased in 5/6 of the subjects with xanthomathosis. Normal cholesterol was combined with increased triglyceride values in 5% of the individuals. A further 6% had normal cholesterol and triglyceride values together with raised LDL cholesterol concentrations, whereas the remaining subjects had normal lipid levels. There was no evidence of homozygosity for the gene(s) for type II hyperlipoproteinaemia. The type III hyperlipoproteinaemia pattern was not seen. Type IIA and IIB electrophoretic patterns were seen in 68 and 13% of those tested, respectively. Changes in lipoprotein patterns with treatment were frequent, especially in males, and the "original" frequency of type IIA is probably higher.