Fumiko Saito

A pedigree of homozygous familial hyperalphalipoproteinemia

A new form of familial lipoprotein disorder, homozygous hyperalphalipoproteinemia (HALP) was studied in one pedigree through three generations. The proband was a healthy male, 50 years old, who was checked for a distinctive elevation of plasma high-density lipoprotein cholesterol (HDL-C) in a routine screening examination. An intensive family study revealed that the proband and one of his sisters were homozygotic carriers of familial HALP judging by their extremely high concentration of HDL-C (181 mg/dL and 163 mg/dL, respectively). In the homozygotes, the lipid composition of HDL was found to be normal while the ratio of HDL lipids to apoproteins A-I and A-II tended to be increased. All five children of the two homozygous individuals and two additional first degree relatives were considered to be heterozygous, since their HDL-C values were moderately elevated, with other lipid levels being normal. The family study thus substantiated the hypothesis, as Glueck et al insisted in 1975, that this lipoprotein disorder is inherited by autosomal dominant transmission. Longevity analysis revealed that the decreased family members showed life prolongation of 9.8 years on an average compared with the appropriate control population of the same district. Our report might be the first to demonstrate the homozygous form of this longevity syndrome.

Further evidence for insulin hypersecretion not as an initial event but as a consequence of body growth and maturation in juvenile-onset obesity

According to our previous study, hyperinsulinism develops not before 10 years of age despite the presence of obesity but during the maturation years of 10-20. We aimed here at examining the growth-related islet B-cell change together with pituitary activity in non-familial juvenile obesity. Measurement of 24 h urine hormones was shown to be useful for evaluation of the diurnal hormones in plasma. In 56 non-obese and obese juveniles, a significantly positive correlation was found between age (6-18 years) and 24 h urine insulin and c-peptide, thus indicating that the age-related absolute value of body weight significantly affects insulin and c-peptide excretions both in non-obese and obese subjects. Consequently, urinary insulin and c-peptide excretions per kg of body weight were highly similar between obese and non-obese juveniles. However, when the lower specific gravity of fat mass compared with lean body mass and the relative shortage of circulating plasma in fat tissues are taken into consideration, it is obvious that obesity by itself specifically augments this physiologic B-cell maturation between 10 and 20 years of age. The possible interactions of growth hormone and pituitary gonadotropin in hyperinsulinism are discussed.

A Pedigree of Homozygous Familial Hyperalphalipoproteinemia

A new form of familial lipoprotein disorder, homozygous hyperalphalipoproteinemia (HALP) was studied in one pedigree through three generations. The proband was a healthy male, 50 years old, who was checked for a distinctive elevation of plasma high-density lipoprotein cholesterol (HDL-C) in a routine screening examination. An intensive family study revealed that the proband and one of his sisters were homozygotic carriers of familial HALP judging by their extremely high concentration of HDL-C (181 mg/dL and 163 mg/dL, respectively). In the homozygotes, the lipid composition of HDL was found to be normal while the ratio of HDL lipids to apoproteins A-I and A-II tended to be increased. All five children of the two homozygous individuals and two additional first degree relatives were considered to be heterozygous, since their HDL-C values were moderately elevated, with other lipid levels being normal. The family study thus substantiated the hypothesis, as Glueck et al insisted in 1975, that this lipoprotein disorder is inherited by autosomal dominant transmission. Longevity analysis revealed that the decreased family members showed life prolongation of 9.8 years on an average compared with the appropriate control population of the same district. Our report might be the first to demonstrate the homozygous form of this longevity syndrome.