Related Experiment Videos
A Japanese family with high density lipoprotein deficiency
Insights
This study identifies two siblings with familial high density lipoprotein (HDL) deficiency, a rare genetic disorder. Their condition presented with extremely low HDL cholesterol and specific apolipoprotein levels, consistent with Tangier disease.
Area of Science:
- Lipid Metabolism
- Genetics
- Biochemistry
Background:
- Familial high density lipoprotein (HDL) deficiency is a rare genetic disorder characterized by severely reduced levels of HDL cholesterol in the plasma.
- Understanding the genetic basis and clinical manifestations of HDL deficiency is crucial for diagnosing and managing related metabolic abnormalities.
Observation:
- Two siblings from a Japanese family presented with markedly reduced plasma HDL (0-1 mg/dl) and very low total cholesterol (30-60 mg/dl).
- Plasma concentrations of apolipoprotein (Apo) A-I and Apo A-II were significantly decreased in the affected siblings.
- Electron microscopy revealed two distinct lipoprotein particle populations in the HDL fraction, and liver biopsy showed lipid deposition in reticuloendothelial cells.
Findings:
- The clinical and biochemical findings in the affected siblings were consistent with homozygous familial HDL deficiency, also known as Tangier disease.
- Parents and some offspring exhibited lower HDL cholesterol levels, suggesting a heterozygote state, though Apo A-I and Apo A-II levels were normal in heterozygotes.
- Plasma low density lipoprotein (LDL) exhibited altered electrophoretic mobility in both patients and heterozygotes compared to normal subjects.
Implications:
- This case highlights the genetic heterogeneity and phenotypic variability within families affected by HDL deficiency.
- Further research into the specific genetic mutations and their impact on lipoprotein metabolism is warranted.
- Understanding these lipid abnormalities may offer insights into cardiovascular disease risk stratification and potential therapeutic targets.
Abstract:
Two siblings with marked reduction of plasma high density lipoprotein (HDL) were found in a Japanese family. Their plasma cholesterol levels were very low (30-60 mg/dl), especially in the HDL fraction (0-1 mg/dl). The concentration of apolipoprotein (Apo) A-I in their plasma was 2-3 mg/dl and that of Apo A-II was 1.5-2.0 mg/dl, determined by means of a single radial immunodiffusion technique. An ultracentrifugally separated HDL fraction contained two different populations of lipoprotein particles, as shown by electron microscopy; a small particle with a diameter of 50-70 A and a relatively large particle at 200 A. Plasma lecithin: cholesterol acyltransferase activity was substantially retained in both cases. Hepatosplenomegaly was present and liver biopsy revealed lipid deposition in reticuloendothelial cells, although the tonsils were apparently normal. No severe atherosclerotic lesions were noticed. The results from these two cases were consistent with the characteristic features of homozygotes of familial HDL deficiency (Tangier disease). HDL cholesterol levels were relatively low in the parents and two children from one patient, which is consistent with the heterozygote state. Two other cases in the kindred were also found to have relatively low HDL cholesterol levels, besides these 4 cases of obligate heterozygotes. Apo A-I and Apo A-II levels in the plasma of the obligate heterozygotes, however, were within the normal range. Plasma low density lipoprotein in the patients moved faster in polyacrylamide gel electrophoresis than those of normal subjects, as did those in the heterozygotes.