INBORN ERROR OF

LIPID METABOLISM
BIOKIMIA II

PRODI KIMIA 2012

Members of Group

Eka Puspa Rini

3325120246

Novia Apriliani
3325122133

Yafie Al Islami
3325122136

Inborn Errors of
Metabolism
Inborn error : an inherited (i.e. genetic) disorder
Metabolism : chemical or physical changes
undergone by substances in a biological system
So, inborn errors of metabolism is any disease
originating in our chemical individuality

Inborn Errors of Lipid

Metabolism
Inborn errors of lipid metabolism occur from a group
of rare genetic disorders in which the body cannot
metabolize lipid component on food normally.
These disorders are usually caused by defects in the
enzymes involved in the biochemical pathways that
break down food components.
Over time, accumulations of fatty substances can be
harmful to many organs of the body. Disorders also
caused by the accumulation of lipids are called
lipidoses.

Inborn Errors of Lipid

Metabolism
1. Gauchers Disease
2. Niemann-Pick disease
3. Tay-Sachs
4. Fabry disease

GAUCHER DISEASE

What is Gaucher Disease?

Gaucher's disease or Gaucher disease (GD) is
a genetic disease in which fatty substances
(sphingolipids) accumulate in cells and certain
organs.

Gaucher Disease
The disease is
caused by a
recessive
mutation in a
gene located on
chromosome 1
and affects both
males and
females.

Why and when is Gaucher Disease

appears?
Gaucher disease caused by a
hereditary deficiency of the
enzyme glucocerebrosidase
(acid beta-glucosidase).
When the enzyme is
defective, lipid called
glucosylceramide
accumulates, particularly in
white blood cells, most often
macrophages (mononuclear
leukocytes).

Acid beta-glucosidase

Where is the disease can be

found?
Gaucher disease is a condition in which
glucocerebroside is formed in the spleen, liver,
kidneys, lungs, brain, and bone marrow.

How do the symptoms of Gaucher

disease?
The disorder is characterized by yellowish-brown
skin pigmentation, bruising, fatigue, anemia, low
blood platelets, and enlargement of the liver and
spleen.

Gaucher Disease

NIEMANN-PICK
DISEASE

What is Niemann-Pick
Disease?
Niemann-Pick Disease is one of a group of
lysosomal storage diseases that affect
metabolism and that are caused by genetic
mutations.
This disease involves dysfunctional metabolism
of sphingolipids, which are fats found in cell
membranes, so it is a kind of
sphingolipidosis.

Niemann-Pick Disease
NiemannPick disease is inherited in an
autosomal recessive pattern, which means
both copies, or alleles, of the gene must be
defective to cause the disease.
Most often, the parents of a child with an
autosomal recessive disorder are carriers:
they have one copy of the altered gene,
but are not affected because the other
copy produces the enzyme.
If both parents are carriers, each
pregnancy has a 25% chance of producing
an affected child.

Why the diseases appears?

NiemannPick disease types A and B caused by mutations in the
SMPD1 (Sphingomyelin phosphodiesterase 1) gene. They stop
the body from making an enzyme, acid sphingomyelinase, that
breaks down lipids.
NiemannPick disease type C (NPC) caused by mutations in
NPC1 or NPC2, which affects a protein used to transport lipids.
Type D was originally separated from type C to delineate a group
of patients with otherwise identical disorders who shared a
common Nova Scotian ancestry. Patients in this group are known
to share a specific mutation in the NPC1 gene, so NPC is used
for both groups.

How do the symptoms of this

disease?

Enlargement of the liver and spleen (hepatosplenomegaly) may

cause reduced appetite, abdominal distension, and pain.
Enlargement of the spleen (splenomegaly) may also cause low
levels of platelets in the blood (thrombocytopenia).

Accumulation of sphingomyelin in the central nervous system

(including the cerebellum) results in unsteady gait (ataxia), slurring
of speech (dysarthria), and difficulty in swallowing (dysphagia).
Basal ganglia dysfunction causes abnormal posturing of the limbs,
trunk, and face (dystonia). Upper brainstem disease results in
impaired voluntary rapid eye movements.

Bones can also be affected: symptoms can include enlarged bone

marrow cavities, thinned cortical bone, or a distortion of the hip
bone called coxa vara. Sleep-related disorders, such as sleep
inversion, sleepiness during the day and wakefulness at night, can
occur.

TAY-SACHS DISEASE

What is Tay-Sachs
Disease?

Tay-Sachs disease (TSD) is a fatal genetic disorder, most

commonly occurring in children, that results in progressive
destruction of the nervous system

The form or type is determined by the age of the individual when

symptoms first appear. Only one form of Tay-Sachs occurs in a
family. If a child has Infantile, older siblings are not at risk to
develop Juvenile or Late Onset Tay-Sachs later in life.
Classic Infantile -symptoms appear around 6 months of age
Juvenile -symptoms typically appear between ages 2 and 5, but
can occur anytime during childhood
Late Onset -symptoms typically appear in adolescence or early
adulthood, but can appear later

Tay-Sachs Disease

Why the Tay-Sachs diseases appears?

People with Tay-Sachs don't
have the DNA instructions
to make Hex-A correctly:
usually they make the HexA, but something is wrong
with the hooks that the cell
uses to move the Hex-A
around inside the cell
Tay-Sachs disease results
fromdefects in a gene on
chromosome 15 that codes
for production of the
enzyme Hex-A. We all have
two copies of this gene.

When is it happen?
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.
It's a disease you get in yourDNAfrom your parents, and
both your mother and your father have to have the
disease in their DNA in order for you to get it.
It is not catching.

Where is the disease started?

Mutations in theHEXAgene disrupt the activity of betahexosaminidase A (prevents the enzyme from breaking
down GM2 ganglioside).
TheHEXAgene provides instructions for making part of an
enzyme called beta-hexosaminidase A, which plays a critical
role in the brain and spinal cord.
This enzyme is located in lysosomes, which are structures in
cells that break down toxic substances and act as recycling
centers.
Within lysosomes, beta-hexosaminidase A helps break down
a fatty substance called GM2 ganglioside.

Where is the disease started?

As a result, this substance accumulates to toxic levels,
particularly in neurons in the brain and spinal cord.
Progressive damage caused by the buildup of GM2
ganglioside leads to the destruction of these neurons,
which causes the signs and symptoms of Tay-Sachs
disease.
Because Tay-Sachs disease impairs the function of a
lysosomal enzyme and involves the buildup of GM2
ganglioside, this condition is sometimes referred to as
a lysosomal storage disorder or a GM2gangliosidosis.

How do the symptoms of this

disease?
Most affected infants have nerve damage starting in utero, with symptoms
appearing at 12 weeks to 24 weeks gestation. Progression is quick and the
child will typically pass away by four or five years old.
Symptoms of Tay-Sachs in infants include:
Deafness
Blindness
Decreased muscle tone
Increased startle response
Paralysis or loss of muscle function
Seizures
Delayed mental and social development
Slow growth
Red spot on the macula (an oval-shaped area near the center of the
retina in the eye)

FABRY DISEASE

What is Fabry Disease?

Fabry disease (FD) is an X-linked genetic disease
caused by a deficiency of the enzyme galactosidase A (-Gal A) in the body. The enzyme
-Gal As function is to break down a fatty
substance called globotriaosylceramide (or GL3).

When is it happen?
When -Gal A is absent, GL3 builds up in the
blood vessel walls throughout the body. As the
abnormal storage of GL3 increases with time, the
bodys blood vessels become narrowed, leading
to decreased blood flow and undernourishment of
the tissues.

Where is the disease can be

found?
This abnormal process occurs in various cell
types and in blood vessels throughout the body,
particularly those blood vessels in the skin,
kidneys, heart, brain and nervous system.

How do the symptoms of this

disease?
The early symptoms of Fabry disease, which usually
begin in childhood, include decreased sweating, heat
intolerance, proteinuria, a reddish-purple skin rash
(angiokeratoma), severe pains in the hands and feet,
hearing loss, chronic fatigue, depression, anxiety,
and gastrointestinal issues such as chronic diarrhea.
Since the disease is progressive, untreated Fabry
disease results in many severe health problems such
as kidney failure, heart problems including
enlargement of the left side of the heart (left
ventricular hypertrophy) and valve disease, and
cerebrovascular problems such as stroke and vertigo.

Pictures of Fabry Victims

Fabry on skin

Fabry on leg

THANK YOU