ABETALIPOPROTEINEMIA
- Genetics and Mechanism
- Autosomal recessive disorder.
- Caused by mutations in the gene encoding the large subunit of microsomal triglyceride transfer protein.
- Leads to abnormal production and secretion of apolipoprotein B (apo B) and apo B–containing lipoproteins.
- Insufficient lipidation of nascent particles prevents normal synthesis and secretion of chylomicrons (intestine) and VLDL (liver).
- Clinical Presentation
- Usually presents in infancy with:
- Fat malabsorption
- Hypocholesterolemia
- Acanthocytosis (crenated RBCs)
- Later in life:
- Deficiencies in fat-soluble vitamins (A, D, E, K)
- Neurologic complications: atypical retinitis pigmentosa, posterior column neuropathy, myopathy
- Retinal changes, peripheral neuropathy, ataxia, lordosis (from muscular weakness), sensory motor neuropathy, mental retardation
- Children appear malnourished, show growth retardation.
- Some develop hepatic steatosis and cirrhosis (possibly related to medium-chain triglyceride therapy).
- Usually presents in infancy with:
- Laboratory Findings
- Absence of plasma apo B–containing lipoproteins
- Extremely low plasma cholesterol (<50 mg/dL)
- Pathophysiology
- Microsomal triglyceride transfer protein is essential for loading triglycerides and phospholipids into the lumen of the endoplasmic reticulum.
- Without it, chylomicrons & VLDL cannot form or be secreted → fat malabsorption & lipid-poor plasma.
- Treatment
- Lipid-poor diet to address digestive intolerance (low daily fat intake, e.g., 5 g/day in children).
- Provide dietary essential fatty acids (e.g., vegetable oils).
- High-dose fat-soluble vitamins (A, D, E, K) supplementation.
TANGIER DISEASE
- Genetics and Mechanism
- Autosomal dominant disorder.
- Mutations in ABCA1 (adenosine triphosphate–binding cassette transporter-1 gene).
- ABCA1 crucial for cholesterol efflux from cells onto nascent HDL → decreased cholesterol efflux → low plasma HDL levels.
- Homozygotes: almost absent plasma HDL.
- Heterozygotes: ~50% normal HDL levels.
- Clinical Presentation
- Named for the kindred on Tangier Island (Chesapeake Bay).
- Orange-colored tonsils (cholesterol deposits).
- Corneal opacities.
- Hepatosplenomegaly (due to foam cell accumulation).
- Peripheral neuropathy.
- Increased risk for premature coronary disease.
- Laboratory Findings
- Very low to absent HDL cholesterol.
- Low total cholesterol.
- Overaccumulation of macrophage cholesteryl esters (foam cells).
- Treatment
- No disease-specific treatment currently available.
- Management focuses on general measures for cardiovascular risk reduction.