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Group 4

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

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

Proteins that bind to fats

transport cholesterol and triglycerides in the

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

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
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


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
Apolipoproteins carry out several roles

they can form the part of structure of

They are cofactor enzymes

act as Ligands for interaction with Lipoprotein
receptors in tissues

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

Cada, Kristian C.
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.  In addition to being abnormal, there
can be fewer red blood cells in circulation
(anemia).   Some of the symptoms of anemia
include being tired, decreased appetite, weakness,
and pale skin.
• Later in life:

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

absorb vitamins A, D, E and K can affect systems of the
•  It appears that many of these symptoms can be
lessened or prevented by medically supervised
fat soluble vitamin supplementation.  This
therapy needs to be managed by a medical team
who is familiar with Abetalipoproteinemia and all
of the issues surrounding the individual patient.
• Spinocerebellar disorder - degeneration of the
cerebellum (an area of the brain) 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.
• 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
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
• 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.
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
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-


• 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
• 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 cholesterol 3.88 – 5.25 0.45

LDL 1.3 – 3.4 0.03

HDL 0.8 – 2.4 0.39

• Symptoms
• Feet numbness
• Occational disability in maintaining
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
• 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