What is Abetalipoproteinemia?

Abetalipoproteinemia is an inherited disorder that impairs the normal absorption of fats and certain vitamins from the diet

What is the Pathology of Abetalipoproteinemia?

The pathology of abetalipoproteinemia is:

-Etiology: The cause of abetalipoproteinemia is by mutations in the MTTP gene, which provides instructions for making a protein called microsomal triglyceride transfer protein. This protein is essential for creating molecules called beta-lipoproteins in the liver and intestine.

-Genes involved: MTTP gene.

-Pathogenesis: The sequence of events that lead to abetalipoproteinemia are: mutations in the gene encoding a subunit of a microsomal triglyceride transfer protein. As a consequence, circulating apoprotein B‐containing lipoproteins are almost completely missing, and the patients are unable to absorb and transport fat and fat‐soluble vitamins.

-Histology: The histology associated with abetalipoproteinemia shows marked fat vacuoles in apical villous cytoplasm, and normal villi.

Abetalipoproteinemia. Very high magnification micrograph of abetalipoproteinemia. Duodenal biopsy. H&E stain. The small bowel mucosa shows the characteristic clear enterocytes (due to lipid accumulation). Brunner's glands are not seen on the images. Related images Intermed. mag. High mag. Very high mag. Nephron. Not altered. CC BY-SA 3.0
Abetalipoproteinemia. Acanthocytosis in a patient with abetalipoproteinemia. Rola Zamel, Razi Khan, Rebecca L Pollex and Robert A Hegele - Not altered. CC BY 2.0
Role of MTP in cellular cholesterol ester biosynthesis. (A) ACAT, a membrane integral enzyme is shown (yellow arrows) to convert free cholesterol present in the endoplasmic reticulum (ER) leaflets into cholesterol esters that remain within the membrane bilayer. MTP is shown to transfer both free cholesterol and cholesterol esters from the ER membranes to apoB-lipoproteins in the ER lumen. It should be pointed out that MTP could transfer both free and esterified cholesterol to apoB that is still associated with membranes. The thickness of orange arrows is meant to show that MTP most likely prefers cholesteryl esters over free cholesterol for transfer. (B) In MTP deficient conditions, transfer of free and esterified cholesterol to apoB-lipoproteins is reduced. Initially this might lead to accumulation of cholesteryl esters. When a high enough concentration of cholesteryl esters is achieved then ACAT activity is inhibited due to product inhibition leading to accumulation of free cholesterol. (C) In the absence of ACAT activity, it is anticipated that cells accumulate more free cholesterol. Indeed, this is known to happen in cells that do not secrete apoB-lipoproteins, such as macrophages. However, in cells that are able to synthesize apoB-containing lipoproteins, MTP can transfer free cholesterol to lipoproteins avoiding excess free cholesterol accumulation in the ER membrane. Multiple functions of microsomal triglyceride transfer protein. Hussain MM, Rava P, Walsh M, Rana M, Iqbal J - Nutrition & metabolism (2012). Not Altered. CC.

How does Abetalipoproteinemia Present?

Patients with disease in lower case typically both males and females present at any age. The symptoms, features, and clinical findings associated with abetalipoproteinemia include failure to gain weight and grow at the expected rate failure to thrive; diarrhea; and fatty, foul-smelling stools steatorrhea.

How is Abetalipoproteinemia Diagnosed?

Abetalipoproteinemia is diagnosed by laboratory tests showing abnormally low cholesterol, and confirmed by genetic testing.

How is Abetalipoproteinemia Treated?

Abetalipoproteinemia is treated by low fat diet and large doses of fat-soluble vitamin.

What is the Prognosis of Abetalipoproteinemia?

The prognosis of abetalipoproteinemia is good. Most individuals with this condition are treated with excess vitamins and a special, fat-controlled diet and have few complications. Untreated individuals with abetalipoproteinemia can develop gradual vision loss, muscle weakness, tremors, and slow or slurred speech that gets worse over time.