ABETALIPOPROTEINEMIA

Group 4
Bustos, Precious Rose
Cabantac, Rhea Katherine
Cabungcal, Kristine
Cada, Kristel Joy
Cada, kristian
Caeg, Anne Clarisse
Calupig, Tiffany Grace
Objectives


Discuss the different types, composition and
synthesis of lipoproteins

Discuss the significance of apolipoproteins

Review the transport of lipids in the blood

Define “abetalipoproteinemia” and its
underlying genetic defect

Explain why intestinal and hepatic cells
accumulating fats in this disorder

Discuss the manifestations and possible
complications of this disorder

Explain why patients with this disorder do not
develop vitamin D deficiency

Discuss other disorders that may arise from
derangements of lipoprotein function, their
etiology and clinical manifestations
Lipoproteins


Combination of lipid and protein serve
as the means of transporting lipids in
the blood
Types and Composition of Lipoprotein
Apolipoproteins


Proteins that bind to fats

transport cholesterol and triglycerides in the
blood

one or more apolipoproteins are present in
each lipoprotein.
Apo E


Present in 3 isoforms: E2, E3, E4

found in Chylomicrons and IDL that binds to
a specific receptor on liver cell

essential for the normal catabolism of
triglyceride-rich lipoprotien constituent

E2 binds poorly to receptors homozygous
poor clearance of chylomicron remnants and
IDL

E4 associated with increased susceptibility to
late onset of Alzheimer’s disease
Apo A1


Major protein component of HDL in plasma

It promotes cholesterol efflux from tissue to
the liver for excretion

It is a co-factor for LCAT (Lecithin
cholesterolacyltransferase)
Apo B


primary apolipoprotiens of LDL “bad
cholesterol,” which is responsible for
carrying cholesterol in the tissue

acts as a ligand for LDL receptors in various
cells throughout the body

High Apo B can lead to plaques that cause
vascular disease leading to heart disease
Different types of apolipoproteins found
on different types of cholesterol
Lipoprotein Apolipoprotein

HDL apoAI, II & IV, apoCI, II & III, apoD

and apoE

LDL apoB100

VLDL apoB100, apoCI, II & III and apoE

Chylomicrons apoAI,II & IV, apoB48, apoCI, II & III,

apoE and apoH

apo B(B-48) that is synthesized in the
intestine, while B-100 is synthesized in liver.

main apolipoprotein of LDL (B- Lipoprotein)
is apolipoprotein B (B-100), which is also
found in VLDL

Apo B-100 is one of the longest single poly
peptide chains known, having 4536 amino
acids
Apolipoproteins carry out several roles


they can form the part of structure of
Lipoproteins

They are cofactor enzymes

act as Ligands for interaction with Lipoprotein
receptors in tissues
 Functions

Apoprotein Lipoprotein Function

B48 CM Carry cholesterol esters

B100 VLDL,IDL,LDL Binds LDL receptor

C-II All Activate LPL

C-III All Inhibit LPL

Apo E CMremn., VLDL,IDL Binds remnant receptor

Apo AI HDL,CM Activates L-CAT

Transport of Lipids in the Blood
The Pathways of Lipid Transport


exogenous pathway

endogenous pathway

pathway of reverse cholesterol transport
Abetalipoproteinemia
(Bassen-Kornzweig syndrome)

CADA, KRISTIAN C.
 MTP gene
• codes (has the DNA sequence) for a protein called
Microsomal Triglyceride Transfer Protein (MTP). 
• expressed in the intestines and liver.
• aid in the transport of triglycerides between
membranes. 
• It helps to deliver these triglycerides to the
developing apolipoproteins B-48 and B-100. 
• Without MTP apolipoproteins B-48 and B-100
cannot form. 
 MTTP Gene

located on the long (q) arm of chromosome 4 at position 24.

 Signs and Symptoms
• In infancy:
• Failure to thrive, or an infant who does not gain
weight and grow as expected.  This can include:
• Diarrhea
• Fatty, foul-smelling stools (steatorrhea)
• Vomiting
• Distention or swelling of the abdomen
• Acanthocytes seen in a blood sample.  These are red
blood cells that have a speculated or “star-like”
appearance. 
• Later in life:

• The vitamin deficiencies due to the body’s inability to

absorb vitamins A, E and K can affect systems of the
body.  
• Spinocerebellar disorder - degeneration of the
cerebellum and spinal cord .
• Retinitis pigmentosa and pigmentary changes in the
retina - abnormalities of the photoreceptors (rods
and cones) of the retina
• Some liver problems have been reported.  At this point
it is unknown how common this feature is.
 Diagnosing Abetalipoproteinemia
• Blood tests as well as a detailed medical history can
help make the diagnosis. 

• The blood tests often show:

 very low serum cholesterol

 absent serum betalipoproteins (VLDLs and LDLs)
 absence of chylomicron fragments
 low serum triglycerides
 fat soluble vitamin deficiencies
   FHBL FHBL  
Abeta Heterozygous Homozygous CMRD
(one mutation) (two mutations)

Eye disorders Reduced or may be Reduced or may Reduced or may be Reduced or may be
eliminated with be eliminated with eliminated with eliminated with
vitamin vitamin vitamin vitamin
supplementation supplementation supplementation supplementation

Fat accumulation        
in liver Some Yes Yes No
Fat accumulation        
in small intestine Yes No No Yes

Gene location   2p24 2p24  

4q22-q24 3p22-p21.1 3p22-p21.1 5q31.1
+ others + others

Inheritance Autosomal Autosomal Autosomal Autosomal

Recessive Dominant Dominant Recessive
Etiology of familial hypocholesterolemia in childhood depending on lipid profile. ABL,
abetalipoproteinemia; AD, autosomal dominant; AR, autosomal recessive; apo AI, apolipoprotein A1; apo B;
apolipoprotein B; HDL, high-density lipoprotein; HBL, hypobetalipoproteinemia; LCAT, lecithin cholesterol
acyltransferase; LDL, low-density lipoprotein; MTP, microsomal triglyceride transfer protein; N, normal; 0, nul; PL,
phospholipids; TC, total cholesterol; CRD, chylomicron retention disease; TG, triglyceride; ↓, few decrease; ↓↓,
significant decrease; ↓↓↓, intense decrease. Peretti et al. Orphanet Journal of Rare Diseases 2010 5:24  
doi:10.1186/1750-1172-5-24
Fat accumulation in the intestine
Abetalipoproteinemia is
associated with fat - soluble
vitamin deficiency
• 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 like beta-
lipoproteins.

• CAEG, ANNE CLARISSE A.

• An inability to make beta-lipoproteins
causes malabsorption of dietary fats and
fat-soluble vitamins.

• 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.
• vitamin E deficient patients are defective in
three steps in the pathway:
1. along with other fat soluble vitamins, the
fat malabsorption decreases the
absorption of vitamin E
2. 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.
3. any vitamin E that is delivered to the liver
also can not be secreted because of the
defect in the VLDL secretion
• Vitamin A and K are also packaged in to
chylomicrons after absorption from the
lumen of the intestine
• 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.
Why do patients with this disorder
do not develop vitamin D
deficiency?
• Vitamin D is a fat-soluble vitamin
• some vitamin D is supplied by the diet, most of
it is made in the body.
• To make vitamin D, cholesterol 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.
• 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.
Disorders may arise from
derangements of lipoprotein function
Case Report

Cabantac, Katherine Rhea D.

 History of Disease
• Routine cholesterol test results

Normal values Lab results

(mmol/L) (mmol/L)
Plasma 3.88 – 5.25 0.45
cholesterol
LDL 1.3 – 3.4 0.03
HDL 0.8 – 2.4 0.39

• Symptoms
• Feet numbness
• Occational disability in maintaining
balance
Past History
• Malabsorption
• Started during childhood
• Mistaken for celiac disease
• Alleviated by less fatty food
• Night vision difficulty
• Gradually deteriorated since age 16
Physical examination
• Decreased deep tendon reflex
• Decreased propioceptive and vibration
senses
• Bilateral pigmented retinopathy
• Gait ataxia
• Positive Rhomberg sign
Additional Laboratory Results
• Increased Prothrombin time
• Decreased Hematocit
• Numerous acanthocytes
• Increased reticulocyte count
• Decreased sedimentation rate
• Small intestines biopsy
• Normal villi with intracellular droplets
positive for fat
Reason for misdiagnosis and late
detection of disease

• Rarity of disease
• Seemingly unrelated symptoms
• Abnormal laboratory results
 Underlying causes
• Absence of apoB lipoprotein
• Malabsorption
• Impaired chylomicron production
• Vit. A deficiency
• Eye problem
• Vit. K deficiency
• Prolonged PT;
• Vit. E deficiency
• Demyelination of long axons
Thank you for Listening…