Abetalipoproteinaemia is a rare autosomal recessive disorder characterised by fat malabsorption, acanthocytosis, ataxia, and retinitis pigmentosa. The biochemical defect is:
- A Mutations in MTP (microsomal triglyceride transfer protein), preventing assembly and secretion of ApoB-containing lipoproteins ✓
- B Absence of apolipoprotein B-48 and B-100 due to mutations in the APOB gene
- C Deficiency of ApoC-II, the obligate LPL activator, causing chylomicron retention
- D Mutations in ApoA-I preventing HDL formation and reverse cholesterol transport
Explanation
Abetalipoproteinaemia is caused by mutations in MTP (microsomal triglyceride transfer protein), not in the APOB gene itself. MTP is required for transferring lipids onto newly synthesised ApoB in the ER, enabling the assembly and secretion of VLDL in the liver and chylomicrons in the intestinal enterocyte. Without MTP, ApoB cannot be lipidated, is misfolded, and undergoes proteasomal degradation. The result is complete absence of ApoB-48 (chylomicrons), ApoB-100 (VLDL, LDL), and near-absent plasma triglycerides and LDL. Fat-soluble vitamin (A, D, E, K) malabsorption underlies the retinitis pigmentosa (vitamin E deficiency) and coagulopathy. Anderson's disease (chylomicron retention disease) involves Sar1b mutations affecting chylomicron secretion specifically from enterocytes.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.