Charles J. Glueck

Neonatal familial type II hyperlipoproteinemia: Cord blood cholesterol in 1800 births

Abstract Umbilical cord blood cholesterol was measured in 1800 consecutive unselected live births in a general hospital. Mean cholesterol (± 1 SD) was 63.8 ± 18.7, range 20–196 mg 100 ml . Cord blood cholesterol levels greater than 100 mg 100 ml (mean cord blood cholesterol ± 2 SD) were arbitrarily identified as elevated. Sixty-five neonates had cord blood cholesterol levels greater than 100 mg 100 ml . Of these 65 infants, both parents could be studied in 26 kindred, the mother only in 23 kindred, and neither parent in 16 kindred. Of the 26 parent pairs, nine mothers and two fathers were found to have Type II hyperlipoproteinemia. Of the 23 mothers of illegitimate, hypercholesterolemic infants, three were found to have Type II hyperlipoproteinemia. An infant and similarly affected mother or father with Type II hyperlipoproteinemia were then identified in 14 of 1800 consecutive live births. Five of ten siblings born to these 14 kindred had Type II hyperlipoproteinemia. Measurement of umbilical cord blood cholesterol in unselected populations offers promise in early diagnosis of neonatal and familial Type II hyperlipoproteinemia and should provide an opportunity for early therapy in a pediatric and young adult population prior to development of symptomatic or anatomic atherosclerosis.

Lipids, Lipoproteins, and Sexual Maturation During Adolescence: The Princeton Maturation Study

Abstract This study encompassed a cross-sectional and longitudinal examination of schoolchildren as they entered into and passed through puberty, examining interrelationships between lipids, lipoproteins, and sexual maturation. In the first year of the study (1976), 529 schoolchildren in grades 5–12 participated; 203 were restudied in 1977, and 141 in 1978. At each yearly visit, the childrens stage of sexual maturation was assessed using the Tanner scale. Plasma cholesterol and triglyceride were quantitated each year; high, low, and very low density lipoprotein cholesterol (C-HDL, C-LDL, C-VLDL) levels were measured in the second and third years of the study. In males, cross-sectional decrements in plasma cholesterol were observed with increasing sexual maturation (Tanner stages 1–4), with an increment at Tanner 5 (sexual maturity); plasma triglyceride levels rose at all stages save Tanner 4. The mid-Tanner fall in plasma cholesterol appears (longitudinally) to be accounted for by reduction in C-HDL, while the rise in plasma cholesterol at Tanner 5 may be produced by an increase in C-LDL. Changes in age and Quetelet indices did not appear to relate closely to changes in C-VLDL in 12- and 13-yr-old males, but increasing age and Quetelet indices in 14–15-yr old males accompanied increasing C-VLDL. Cross-sectional studies in females revealed that plasma cholesterol fell at Tanner stages 3 and 4 and rose at stage 5; plasma triglyceride rose during all stages except Tanner 4. Longitudinal studies suggested that the decrements in plasma cholesterol in females may be partially accounted for by reductions in C-HDL; the increase in plasma cholesterol in late sexual development may be accounted for by an increase in C-LDL. In male children, we speculate that the fall in C-HDL and late rise in C-LDL as sexual maturation progresses is associated with increased testosterone production.

Plasma cholesterol and triglyceride levels in 6775 school children, ages 6–17

Associations of age, sex, and race with the distribution of fasting plasma cholesterol and triglyceride were studied in 6775 school children (4946 white and 1829 black students, ages 6–17 yr) in a biethnic school district. The target population included 8906 students with 84% of eligible white and 78% of eligible black children participating. In children ages 6–10, mean cholesterol and triglyceride levels varied only minimally. Females 6–10 yr old generally had higher mean plasma cholesterol and triglyceride than males, and blacks had higher mean cholesterol and lower mean triglyceride than whites, p < 0.001. In comparison to the cross-sectional stability of cholesterol and triglyceride over ages 6–10, plasma cholesterol began to fall at ages 11 and 12, continued to fall through ages 15–16, and rose at age 17. An inverse pattern was observed for mean triglycerides. The major increment in triglyceride levels occurred between the ages of 11 and 12, temporally concordant with decrements in cholesterol. Subsequently, in males mean triglycerides continued to rise through age 17, while in females mean triglycerides dipped sharply at ages 16 and 17. Withinrace comparisons of changes in triglyceride over age show the males first having lower triglyceride than females at ages 11–13, and the female levels falling below the male levels at ages 15–17. The decrements of cholesterol and increments in triglyceride during adolescence were also generally observed for the extremes of the distribution, the 5th and 95th percentiles. As was the case for 6–11-yr olds, in the 12–17-yr-old children, blacks had higher mean cholesterols and lower mean triglycerides than whites. Within the limitations of the cross-sectional nature of this study, the inverse changes of cholesterol and triglyceride suggest that hormonal and growth changes during adolescence may have a notable effect on plasma lipids. The availability of age-, sex-, and race-specific cholesterol and triglyceride distributions may allow more meaningful assessment of plasma cholesterol and triglyceride levels of any individual child.

Estrogen-induced pancreatitis in patients with previously covert familial Type V hyperlipoproteinemia☆

Abstract Previously covert familial Type V hyperlipoproteinemia became overt in three women and one man, when pancreatitis followed postmenopausal and postprostatectomy estrogen administration. Exogenous and endogenous hypertriglyceridemia were severely exacerbated, carbohydrate tolerance worsened, and activity of postheparin lipolytic enzymes were depressed by estrogenic “therapy”. Amelioration of pancreatitis, decrements in hyperglyceridemia and hyperglycemia, and increments in postheparin lipolytic activities followed cessation of estrogens.

Lipid and lipoprotein distributions in white children ages 6–19 yr. The lipid research clinics program prevalence study☆

Abstract Cross-sectional age- and sex-specific distributions of plasma lipids and lipoproteins are described for 1402 white children ages 6–19 yr. These children were part of a random sample examined at seven lipid research clinics (LRC) during the LRC Prevalence Study, which was established to determine the prevalence of hyperlipidemias and to describe the distribution of lipids and lipoproteins in diverse populations. These populations were not selected to be representative of the entire North American pediatric population. Nonetheless, the large numbers of children in the seven LRC populations and their socioeconomic and geographic diversity do permit analytical and comparative studies of physiological and sociodemographic variables in school-age children. This report of their lipid and lipoprotein levels is one in a series of such studies. Examination of the distribution of plasma lipids and lipoproteins showed that total cholesterol (TCH) and low-density lipoprotein cholesterol (LDL-c) were lower in males than females in most age groups studied. The difference in LDL-c is most marked in the younger age group (ages 6–9 yr) and accounts for most of the difference in TCH concentration at this age. During the adolescent period (ages 10–14 yr) a decline in high-density lipoprotein cholesterol (HDL-c) concentration occurs in the males, but not in the females. This decline continues throughout the postadolescent (ages 16–19 yr) period. The resulting difference in HDL-c mainly accounts for the higher TCH observed in the 16–19 yr-old females. Our study confirms the fall in TCH concentration at about adolescence described previously. However, it highlights the different mechanisms responsible in the two sexes. Whereas in the males the decline in TCH is mainly the result of reduction in the concentration of HDL-c, in the females it is due mainly to a gradual decline in LDL-c.

Primary and familial hypoalphalipoproteinemia

Our specific aim was to assess within-family clustering of high-density lipoprotein cholesterol (HDLC) levels in kindreds identified through probands with primary hypoalphalipoproteinemia, and to determine whether, and to what degree, familial aggregation of HDLC less than or equal to the tenth percentile represents a heritable trait, familial hypoalphalipoproteinemia. Our probands were selected arbitrarily by virtue of HDLC less than or equal to the age-sex-race-specific tenth percentile as the sole dyslipoproteinemia, with an additional requirement that they be normotriglyceridemic (triglyceride levels less than the 90th percentile). The probands were also required to have primary hypoalphalipoproteinemia, not secondary to diseases and/or drugs. Fifteen of the 16 probands were men; 12 were referred because of premature myocardial infarction, angina, or stroke, 2 because of family history of premature myocardial infarction or stroke, and 2 because of low HDLC observed on routine health examinations. Two of the 16 kindreds exhibited three-generation vertical transmission of bottom decile HDLC. In three kindreds, there was also three-generation vertical transmission of bottom decile HDLC, but top decile triglycerides accompanied bottom decile HDLC in one or more generations. Eight kindreds displayed two-generation vertical transmission of bottom decile HDLC. After excluding probands, there were 11 critical matings (bottom decile HDLC by normal), with 30 living offspring, all of whom were sampled. Of these 30 offspring, 13 had bottom decile HDLC, 17 had HDLC greater than tenth percentile. The ratio of offspring with bottom decile HDLC to those of HDLC greater than tenth percentile was 13:17 (0.76/1), not significantly different from the ratio of 1/1, the ratio predictive of a dominant trait, X2(1) = 0.53, P greater than 0.4. The nearly 1:1 segregation ratio for the group of offspring was not due to the aggregation of sibships with, in general, most of the sibs, or none of the sibs affected; within-family expression of low HDLC was also not sex-linked. The 13 hypoalphalipoproteinemic offspring of 11 critical matings included only two subjects whose bottom decile HDLC was accompanied by top decile triglyceride. Our data suggests that not only (by selection) was low HDLC in the probands the sole dyslipoproteinemia, but that the segregation of low HDLC in offspring of critical matings was primarily accounted for by isolated low HDLC, not by hypoalphalipoproteinemia secondary to hypertriglyceridemia. Familial hypoalphalipoproteinemia is a heritable disorder with a pattern of transmission not significantly different from that expected by a hypothesis of mendel

Hyperalpha- and hypobeta-lipoproteinemia in octogenarian kindreds☆

Abstract To assess factors related to distinctive longevity, lipoprotein and kindred studies were carried out in 22 octogenarian kindreds self-referred by virtue of either two siblings or a parent and child living to age 80 or over. There was evidence for familial hyperalpha-lipoproteinemia in 7 kindreds, for familial hypobeta-lipoproteinemia in 3 kindreds, and for primary hyperalpha-lipoproteinemia and hypobeta-lipoproteinemia in an additional 2 and 2 kindreds respectively. First degreee relatives of probands with primary or familial hyperalpha- or hypobeta-lipoproteinemia had sharply reduced morbidity and mortality from myocardial infarction when compared to population controls, P P P

Familial hyper-alpha-lipoproteinemia in 26 kindreds

The inheritance of familial hyper‐alpha‐lipoproteinemia was investigated in 161 individuals in 11 black kindreds and 15 white kindreds. After age and sex adjustment, the distribution of high density lipoprotein‐cholesterol (C‐HDL) in the relatives of probands was examined for evidence of bimodality. In whites, bimodality appeared to be present, with one mode at about 46 mg/dl and the other at about 69 mg/dl. In blacks, there was little convincing evidence of bimodality. In the white kindreds, it appeared that one factor with a relatively large effect is causing the familial aggregation of high C‐HDL levels; this factor could be a major gene.

Parent-offspring and sibling lipid and lipoprotein associations during and after sharing of household environments: the Princeton school district family study.

Abstract The specific aim of this report was to determine whether, and to what degree, parent-offspring and sibling associations for lipids and lipoproteins outlast the period of shared household environment. Intrafamilial lipid-lipoprotein associations were assessed in two and three generation kindreds in the Cincinnati Lipid Research Clinics Princeton School District Family Study. Intrafamilial lipid-lipoprotein associations were evaluated in parents and their pediatric (

Benign symmetric lipomatosis (Launois-Bensaude adenolipomatosis) with gout and hyperlipoproteinemia.

Abstract A thirty year old woman with Launois-Bensaude adenolipomatosis, a disease characterized by diffuse symmetric deposits of adipose tissue on the neck, back and upper trunk, has been studied. Gouty arthritis developed at age seventeen, and oligomenorrhea and muscle cramps were prominent symptoms. Pes cavus and extensor plantar reflexes were present. Metabolic studies with the patient on a purine-free diet demonstrated hyperuricemia, a marked increase in the whole body miscible pool and daily turnover of uric acid, augmented extrarenal disposal of uric acid and excessive incorporation of glycine-1- 14 C into urinary uric acid. Azathioprine therapy resulted in moderate suppression of purine synthesis; this suppression was not as marked as that observed in gouty patients studied previously. Glucose tolerance in this patient was abnormal, and immunoreactive insulin response during an oral glucose tolerance test was exaggerated. Plasma triglyceride levels were elevated, and a type IV lipoprotein pattern was present. The patients sister had a similar symmetric lipomatosis, elevated uric acid to creatinine ratio in the urine, hypertriglyceridemia and type IV lipoprotein pattern on electrophoresis.