Am I having Tangiers

disease ?

Problem Statement

A form 6 students share a news with you.

I am shocked when I look at my blood test result. My blood total

cholesterol is more than 300 mg/dL, the LDL cholestrol is be more
than 220 mg/dL but my triglyceride levels tend to be normal,
which are below 150 mg/dL. I am still young! I have a healthy life
because I do not want to be like my mother who is having
hypercholestrol. Am I having Tangiers disease. Explain him
the condition and things he can do to help himself. Explain
what is Tangiers disease too.

Analysis Case
Total cholesterol=
more than 300mg/dL
LDL cholesterol=
more than 220 mg/dL
Triglyceride level=
below 150 mg/dL
Mother having
hypercholesterol
Still young
Have healthy lifestyle

FOCUS
. What is Tangiers disease ?

2. Why blood cholesterol is higher in familial

hypercholesterolemia ?

Focus 1 : What is Tangiers

disease ?
- Autosomal recessive genetic
disorder which is the condition of
almost completely absence of HDL
(high density level) that
functioning as attaching with
cholesterol in order for breaking
down at liver.

WHAT CAUSES TANGIER

DISEASE?
Tangier disease due to mutation in
ABCA1 gene which official name is
ATP binding cassette subfamily A
member 1., which provides
instructions for making proteins that
transport molecules across cell
membrane.

WHERE IS THE ABCA1

GENE LOCATED?

The ABCA1 gene is located on the long (q) arm of chromosome 9 at position
31.1.
More precisely, the ABCA1 gene is located from base pair 104,781,002 to base
pair 104,928,246 on chromosome 9.

WHAT IS THE
IMPORTANCE OF ABCA1
GENE?
ABCA1 gene provides instructions making
proteins that transport molecules across
membranes.
The ABCA1 protein is produced in many tissues,
with high amounts found in the liver and in
immune system cells called macrophages.
This protein moves cholesterol and certain fats
called phospholipids across the cell membrane
to the outside of the cell.
These substances then picked up by a protein
called apolipoprotein and combine to make highdensity lipoprotein (HDL).

CHOLESTEROL BECAUSE HIGH LEVELS OF

THIS SUBSTANCE REDUCE THE CHANCES OF
DEVELOPING

HEART

AND

BLOOD

VESSEL

DISEASE.
HDL

IS

MOLECULE

CHOLESTEROL

AND

THROUGH

THE

BODYS

TISSUES

THE

PROCESS

THAT

PHOSPHOLIPIDS

BLOODSTREAM
OF

CARRIES

TO

FROM

THE

THE

LIVER.

REMOVING

EXCESS

CHOLESTEROL FROM CELLS IS EXTREMELY

IMPORTANT FOR BALANCING CHOLESTEROL
LEVELS AND MAINTAINING CARDIOVASCULAR

HDL (High-Density
Lipoprotein) the good
cholesterol

BIOCHEMICAL SIGNS OF
TANGIER DISEASE
HDL concentrations= less than 5mg/dL
Low total cholesterol= below 150mg/dL
Normal or high triglycerides= more than or equal
to 150mg/dL

Sign and Symptom of

Tangier Disease

Risk of cardiovascular disease

Slightly elevated amount of fat in the blood
Disturbance in nerve function
Enlarged body
Orange-colored tonsils
Often develop atherosclerosis that is
accumulation of fatty deposits and scar-like tissue
in the lining of the arteries
Enlarged spleen
Enlarged liver
Corneal clouding
Type 2 diabetes

to boost
uppump
the HDL
level
How
Exercise
(can help
up HDL
)
Quit smoking
Healthy weight ( avoid obesity )
medications
Niacin-to increase HDL cholesterol and
have least side effects.
Fibrates- medications fenofibrate and
gemfibrozil can help increase HDL
cholesterol level
Statins-block a substance liver needs to
make cholesterol and this will reduces
cholesterol in liver cells which causes
liver to remove cholesterol from blood.

FOCUS 2 :Why blood

cholesterol is higher in
familial
- Alteration of gene on chromosome
hypercholesterolemia
? of
number
19 containing information
protein, LDL receptor responsible to
clear up LDL cholesterol
The defect makes the body unable to
remove low density lipoprotein (LDL, or
"bad") cholesterol from the blood. The
condition is typically passed down
through families in an autosomal
dominant manner which means only
inherit abnormal gene from one parent

WHAT IS
HYPERCHOLESTEROLE
MIA ? is a condition characterized by very
Hypercholesterolemia
high levels of cholesterol in the blood
People with hypercholesterolemia have a high risk of
developing a form of heart disease called coronary artery
disease.
This condition occurs when excess cholesterol in the
bloodstream is deposited in the walls of blood vessels,
particularly in the arteries that supply blood to the heart
(coronary arteries)
The abnormal buildup of cholesterol forms clumps (plaque)
that narrow and harden artery walls. As the clumps get
bigger, they can clog the arteries and restrict the flow of blood
to the heart

OTHER PROBLEMS ?
health problems related to the buildup of excess
cholesterol in other tissue
If cholesterol accumulates in tendons, it causes
characteristic growths called tendon xanthomas
Yellowish cholesterol deposits under the skin of
the eyelids are known as xanthelasmata

WHAT ARE GENES

AFFECTING THEM ?
1. APOB,
2. LDLR,
3. LDLRAP1,
4. PCSK9

TALKING ABOUT
LDLRAP1
GENE..is caused by
When hypercholesterolemia
mutations in the LDLRAP1(Low-density lipoprotein receptor
adapter protein 1) gene,
the condition is inherited in an autosomal
recessive pattern.
Autosomal recessive inheritance means the
condition results from two altered copies of the
gene in each cell. The parents of an individual
with autosomal recessive hypercholesterolemia
each carry one copy of the altered gene, but their
blood cholesterol levels are usually in the normal
range.

MUTATIONS IN THE
LDLR GENE
Those who suffers familial hypercholestrolemia have
mutations in the LDLR gene that encodes the LDL
receptor protein, which normally removes LDL from
circulation.
Some of these genetic changes reduce the number
of low-density lipoprotein receptors produced within
cells.
Other mutations disrupt the receptors ability to
remove low-density lipoproteins from the blood.

"Autosomal" means that the gene in question is

located on one of the numbered, or non-sex,
chromosomes.
"Dominant" means that a single copy of the
disease-associated mutation is enough to cause the
disease.

Sign and symptom

Hereditary. It can be from heterozygous parent

but if homozygous parent, its the worst.
Heart disease at young age
Angina from heart disease
Xanthomas (fatty skin deposits) on the elbows,
buttocks, knees, and tendons
Cholesterol deposits around the eyelids, also
known as xanthelasmas
Cholesterol deposits around the corneas, also
known as corneal arcus

How it can diagnosed

From blood test
Total cholesterol:
in children, it will be more than 250
mg/dL
in adults, it will be more than 300 mg/dL
LDL cholesterol:
in children, it will be more than 170-200
mg/dL
in adults, it will be more than 220 mg/dL
The doctor will also test triglycerides,
which are made up of fatty
acids.Triglyceride levels tend to be
normal in patients with this genetic

SIMILARITIES BETWEEN
TANGIER DISEASE AND
FAMILIAL
HYPERCHOLESTEROLEMIA
@Same blood test result:
High LDL level
Normal triglyceride levels

@Low level of HDL

@Genetic disorder

Different tangier and

familial
hypercholesterol
Tangier
disease
Familial hypercholesterolemia
Due to mutation in ABCA1
gene

Due to mutation in LDLR gene.

Autosomal recessive

It can be from heterozygous

parent. But if homozygous, it
more critical
Autosomal dominant
High LDL
Lack of LDL receptor make
LDL not transported from the
bloodstream.
either male or female carry
mutated LDLR gene

Low HDL
Less of transport of
cholesterol from bloodstream
both parents have carry
mutated ABCA1 gene

CONDITION
The signs and symptoms of Tangiers disease and
familial hypercholestrolemia are almost similar. But,
He does not have Tangier Disease, because:

@ he does not have mild hypertriglycemia

@ he does not experienced any physical symptoms
such as
cloudy cornea, enlarged tonsils, orange or yellow
tonsils
@ he does not experienced any internal defects such
as
enlarged spleen or liver and premature
ather0sclerosis

Conclusion

He have familial hypercholesterolemia. Because:

Have high LDL (Low Density Lipoprotein)
Total of cholesterol more than 300 mg/dL
Mother have hypercholesterolemia and this is
inherited disease.
Still
young.
Symptom
of
familial
hypercholesterolemia is get disease in young
age.
Have
healthy
lifestyle.
Being
familial
hypercholesterolemia is not mean not have
healthy lifestyle.
Action must take is
Make therapy with doctor
Change to healthy dietary.