Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

HDL Deficiency, primary (Hypoalphalipoproteinemia) [E78.6]

OMIM numbers: 604091, 606967 (LCAT), 107680 (APOA1), 600046 (ABCA1)

Dr. med. Hanns-Georg Klein

Scientific Background

Primary hypoalphalipoproteinemia (HDL cholesterol < 10 mg/dl) is caused by a defect in the formation, maturation or metabolism of HDL particles. Immature HDL precursors in the plasma and lipid deposition in parenchymatous organs and the cornea (corneal opacity, not be mixed up with arcus lipoides) are typical signs of HDL deficiency. In essence, mutations in 3 genes are causing the disorder:

  1. Lecithin cholesterol acyltransferase (LCAT), a glycoprotein formed and secreted by the liver, is responsible for the esterification of free cholesterol in the plasma. Mutations in the LCAT gene lead to LCAT deficiency or Fish Eye Disease. The coronary risk is thought to be elevated in homozygous carriers.
  2. Apolipoprotein A-I (Apo A-I), a structural protein of HDL particles, is the most important co-factor of the LCAT activation. Apo A-I deficiency has been associated with a significantly elevated risk for CHD.
  3. ATP-binding Cassette Transporter-1 (ABCA1), a membrane protein, is involved in the cholesterol efflux from the cell. Mutations in the ABCA1 gene lead to the rare Tangier disease characterized by orange tonsils, hepatosplenomegaly and neuropathy. The coronary risk is moderately increased.