This document discusses abetalipoproteinemia, a rare genetic disorder characterized by the lack of apolipoprotein B, which is necessary for the formation of chylomicrons, VLDLs, and LDLs. This leads to an inability to absorb and transport dietary fats and fat-soluble vitamins. Patients with abetalipoproteinemia experience fat accumulation in intestinal and liver cells, malabsorption of fat and fat-soluble vitamins like vitamin E, and associated neurological and vision complications. The underlying genetic defect is mutations in the microsomal triglyceride transfer protein gene, which is essential for producing beta-lipoproteins needed for fat absorption and transport.

1. ABETALIPOROTIENEMIA GROUP 3 Kavita Narula Arsenio Reblando Jinky Harvey Shila Lacia Dexcel Petty

3. Lipoproteins

5. Density (g/m L ) Class Diameter (nm) % protein % cholesterol % phospholipid % triacylglycerol >1.063 HDL 5-15 33 30 29 8 1.019-1.063 LDL 18-28 25 50 21 4 1.006-1.019 IDL 25-50 18 29 22 31 0.95-1.006 VLDL 30-80 10 22 18 50 <0.95 Chylomicrons 100-1000 <2 8 7 84

31. 3. Review the transport of lipids in the blood

33. Types of blood lipoproteins • Chylomicron (formed in cells of the small intestine) transfers dietary lipids from the intestine into the liver. • VLDL (formed in the liver) transfers lipids from the liver by blood to extra-hepatic tissues. • IDL (formed in circulation) is an intermediate LP of VLDL breakdown • LDL (formed in circulation) transfers lipids from blood into tissues. • HDL (formed in the liver and small intestine) transfers lipids from extra-hepatic locations to the liver.

37. 4. Define “abetalipoproteinemia”. What is the underlying genetic defect?

40. 5. Why are the intestinal and hepatic cells accumulating fats in this disorder? 6. What is its manifestations and possible complications?

44. 7. Abetalipoproteinemia is associated with fat soluble vitamin deficiency. Explain this statement.

45. Abetalipoproteinemia is an inherited disorder that affects the absorption of dietary fats, cholesterol, and fat-soluble vitamins. People affected by this disorder are not able to make certain lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood. Specifically, people with abetalipoproteinemia are missing a group of lipoproteins called beta-lipoproteins.

46. An inability to make beta-lipoproteins causes severely reduced absorption (malabsorption) of dietary fats and fat-soluble vitamins (vitamins A, K, and E) from the digestive tract into the bloodstream. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues, particularly nerve cells and tissues in the eye.

47. Patients with abetalipoproteinemia develop severe vitamin E deficiency because they are defective in three steps in this pathway: First, along with other fat soluble vitamins, the fat malabsorption decreases the absorption of vitamin E Second, the small amount of vitamin E that maybe absorbed can not be efficiently secreted by the intestine because of the defect in the chylomicron secretion. Third, any vitamin E that is delivered to the liver also can not be secreted because of the defect in the VLDL secretion

48. Vitamin A and K Aare also packaged in to chylomicrons after absorption from the lumen of the intestine, but unlike vitamin E , they have a separate transport system in the blood and are not dependent on VLDL for their transport. Because the absorption of these vitamins is affected only at steps 2 and 3. that’s why deficiency of these fat soluble vitamins are not severe.

49. 8. Why do patients with This disorder do not develop vitamin D deficiency?

50. Vitamin D is a fat-soluble vitamin, meaning it is able to be dissolved in fat. While some vitamin D is supplied by the diet, most of it is made in the body. To make vitamin D, cholesterol, a sterol that is widely distributed in animal tissues and occurs in the yolk of eggs, as well as in various oils and fats, is necessary. Once cholesterol is available in the body, a slight alteration in the cholesterol molecule occurs, with one change taking place in the skin. This alteration requires the energy of sunlight (or ultraviolet light). Vitamin D deficiency, as well as rickets and osteomalacia, tends to occur in persons who do not get enough sunlight and who fail to eat foods that are rich in vitamin D.

51. Once consumed, or made in the body, vitamin D is further altered to produce a hormone called 1,25-dihy-droxy-vitamin D (1,25-diOH-D). The conversion of vitamin D to 1,25-diOH-D does not occur in the skin, but in the liver and kidney. First, vitamin D is converted to 25-OH-D in the liver; it then enters the bloodstream, where it is taken-up by the kidneys. At this point, it is converted to 1,25-diOH-D. Therefore, the manufacture of 1,25-diOH-D requires the participation of various organs of the body—the liver, kidney, and skin.

52. The purpose of 1,25-diOH-D in the body is to keep the concentration of calcium at a constant level in the bloodstream. The maintenance of calcium at a constant level is absolutely required for human life to exist, since dissolved calcium is required for nerves and muscles to work. One of the ways in which 1,25-diOH-D accomplishes this mission is by stimulating the absorption of dietary calcium by the intestines .

53. Approximately 80% is absorbed into the lymphatic system. Vitamin D is bound to vitamin D-binding protein in the blood and carried to the liver where it undergoes its first hydroxylation into 25-hydroxyvitamin D. This is then hydroxylated in the kidney into 1,25(OH)2D. When there is a calcium deficiency, parathyroid hormone is produced, which increases the tubular reabsorption of calcium and renal production of 1,25(OH)2D. The 1,25(OH)2D travels to the small intestine and increases the efficiency of calcium absorption. That is why vitamin D deficiency is not manifested in this disorder because it is not solely dependant on lipoproteins.

54. 9. Aside from abetalipoproteinemia, what other disorders may arise from derangements of lipoprotein function? Discuss their genetic etiology and clinical manifestations.