Tuesday, April 15, 2014

Two major isoforms of human apolipoprotein (apo) B have been identified, apo B-48 and apo B-100. The apoB-100 consists of 4,536 amino acids and is one of the largest proteins secreted by the liver in the form of VLDL. The small intestine secrets chylomicrons which contains the amino-terminal 2152 amino acids of apo-B100, is synthesized as a result of an apo-B mRNA-editing. Apolipoprotein B mRNA editing is a zinc-dependent and its metabolism may be affected when utilizing a diet low in zinc to induce zinc deficiency. The Human Apolipoprotein B48 (APOB48) ELISA method has been employed for determining the in vitro quantitative measurement of human APOB48 in serum, plasma and other biological fluids.

The function of apoB-48 isoform is in fat absorption of the small intestine, transport dietary fat in the circulation and is involved in the synthesis, assembly and secretion of chylomicrons. Thus apoB-48 can serve as a suitable marker for clinical studies of postprandial lipoproteins and related cardiovascular risk. Clinical studies indicate that elevated concentrations of plasma apoB48 in adults are associated with the development of atherosclerosis.

Apo-lipoprotein B48 deficiency in human leads to the development of abetalipoproteinemia also known as Bassen–Kornzweig syndrome. It is an inherited disorder caused by a mutation in the gene encoding the microsomal triglyceride transfer (MTTP) protein. MTTP is an endoplasmic reticulum protein that transfers triglycerides to apolipoprotein B-48 (apoB48) in the enterocyte. The mutation in MTTP prevents apoB48 from combining with triglycerides to form chylomicrons. The absence of functioning chylomicrons causes severe mal-absorption of dietary fats and fat-soluble vitamins (vitamins A, D, E, and K) from the digestive tract into the bloodstream leading to hypolipidemia, fat malabsorption, and neurologic disorders.

The signs and symptoms of abetalipoproteinemia appear in the first few months of life because pancreatic lipase is not active in this period. They can include failure to gain weight and grow at the expected rate (failure to thrive in infancy); diarrhea; abnormal star-shaped red blood cells (acanthocytosis); and fatty, stool abnormalities, including: fatty stools that appear pale in color, frothy stools and abnormally foul-smelling stools (steatorrhea). Other features of this disorder may develop later in childhood and often impair the function of the nervous system. Disturbances in nerve function may cause affected people to eventually develop poor muscle coordination and difficulty with balance and movement (ataxia). Curvature of spine, protruding abdomen and slurred speech can also appears in the late 10 years of life people with abetalipoproteinemia. Individuals with this condition may also develop an eye disorder called retinitis pigmentosa, in which progressive degeneration of the light-sensitive layer (retina) at the back of the eye can cause vision loss. Adults in their thirties or forties may have increasing balance and coordination difficulties. In addition many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially a deficiency of vitamin E. Diagnosis of abetalipoproteinemia typically consists of stool sampling, a blood smear, and a fasting lipid panel though these tests are not confirmatory. As the disease is rare, though a genetics test is necessary for diagnosis, it is generally not done initially.

This syndrome is a rare disease passed down through families that more often affects males. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Abetalipoproteinemia is a rare disorder with approximately 100 cases described worldwide.

The standard treatment involves fat-restricted diets and fat-soluble vitamin supplementation involving massive amounts of vitamin E and A. Vitamin E contributes the body restore and produce lipoproteins, which people with abetalipoprotenimia usually lack. Vitamin E also helps keep skin and eyes healthy; studies show that many affected males will have vision problems later on in life. Developmental coordination disorder and muscle weakness are usually treated with physiotherapy or occupational therapy. Dietary restriction of triglycerides has also been useful. If treatment is initiated early in disease the neurologic sequelae may be reversed and further deterioration can be prevented. High doses of vitamin A may slow retina damage and decreased vision.

On the other hand, the lack of functional MTP and mutation in the apoB100 gene results in an inability of the liver to synthesize very-low-density lipoproteins (VLDL). The impaired synthesis of VLDL results in the accumulation of triglycerides within hepatocytes and results in significant Familial hypobetalipoproteinemia, nonalcoholic fatty liver disease and hepatic steatosis. Hence the clinical features of abetalipoproteinemia and familial hypobetalipoproteinemia are similar to those of celiac disease it is not to be confused with Celiac disease.

In contrast to Abetalipoproteinemia, hypobetalipoproteinemia is a genetic disorder that can be caused by a mutation in the ApoB gene results in an lack production of Apo-B48. Interestingly, longevity is reportedly associated with hypobetalipoproteinemia, probably because the lowered serum cholesterol in FHBL protects against cardiovascular diseases.

In conclusion, lack of Apo-B48 is implicated in the development of Abetalipoproteinemia. Knowledge in the biology of lipoprotein metabolism has expanded significantly in the past two decades. Such knowledge will prepare us to better understand Abetalipoproteinemia. More research is needed to comprehensively identify these causes in order to further strengthen clinicians’ toolkit for the diagnosis of Abetalipoproteinemia.


R W Milne, P K Weech, L Blanchette, J Davignon, P Alaupovic, and Y L Marcel (). Isolation and characterization of apolipoprotein B-48 and B-100 very low density lipoproteins from type III hyperlipoproteinemic subjects. J Clin Invest. Mar 1984; 73(3): 816–823.

Scott K. Reaves, Jessica C. Fanzo, John Y. J. Wu, Yi Ran Wang, Yan W. Wu, Lei Zhu, and Kai Y. Lei. (). Plasma Apolipoprotein B-48, Hepatic Apolipoprotein B mRNA Editing and Apolipoprotein B mRNA Editing Catalytic Subunit-1 mRNA Levels Are Altered in Zinc-Deficient Rats. J. Nutr. October 1, 1999 vol. 129 no. 10 1855-1861

M.M.U. Nzekwu, G.D.C. Ball, M.M. Jetha, C. Beaulieu and S.D. Proctor. Apolipoprotein B48: a novel marker of metabolic risk in overweight children? Biochemical Society Transactions (2007) Volume 35, part 3 484-486


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