Aetiology
Mutations in the microsomal triglyceride transfer protein (MTTP) gene localised on chromosome 4 causes abetalipoproteinaemia and results in low or absent plasma levels of apolipoprotein B and LDL-cholesterol.[1][3][6][7][9][10][11][12] As the disorder is recessive, both copies of the gene must be faulty in order for the disease to present clinically. Genetic mutations of apolipoprotein B gene are seen in homozygous hypobetalipoproteinaemia but not abetalipoproteinaemia.[3]
Pathophysiology
After ingestion, lipids are processed for absorption across intestinal cells into the blood through a process that requires a chaperone protein (microsomal triglyceride transfer protein [MTTP]) and an acceptor protein (apolipoprotein B [apo B]).[13] MTTP transfers lipids to apo B in enterocytes and hepatocytes and promotes the assembly of lipoproteins that transport triglyceride, cholesterol ester, and fat-soluble vitamins. In abetalipoproteinaemia, the gene coding for MTTP is abnormal and MTTP is either absent or non-functional. As a result, lipoprotein assembly and secretion from the intestine is defective, leading to fat malabsorption.[14] As bowel epithelial cells are unable to place fats into transfer complexes, lipids accumulate in the intestinal lumen, and fat malabsorption results. Additionally, lipids may accumulate in liver cells (hepatic steatosis). Defective lipoprotein secretion from the liver results in steatosis which may progress to cirrhosis.[15][16][17][18]
Fat-soluble vitamins found in ingested foods and vitamin supplements cannot be absorbed due to the same faulty fat-transfer process. Consequently, calorie and vitamin deficiencies lead to poor weight gain and faltering growth.[1] Vitamin E deficiency is particularly concerning due to the consequence of demyelinisation of the peripheral nervous system and the posterior columns of the spinal cord. Neurological, muscular, and ocular abnormalities result.[2][3][19]
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