DISORDERS OF LIPID METABOLISM

INBORN ERROR OF LIPID METABOLISMBIOKIMIA II

PRODI KIMIA 2012

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Novia Apriliani3325122133Eka Puspa Rini3325120246Yafie Al Islami3325122136

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

Inborn Errors of MetabolismInborn Errors of Lipid MetabolismInborn 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.Gauchers DiseaseNiemann-Pick diseaseTay-SachsFabry diseaseInborn Errors of Lipid MetabolismGAUCHER DISEASEWhat 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 DiseaseThe disease is caused by a recessive mutation in a gene located on chromosome 1 and affects both males and females. 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).Why and when is Gaucher Disease appears?

Acid beta-glucosidaseWhere 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 DISEASENiemann-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.What is Niemann-Pick Disease?Niemann-Pick DiseaseNiemannPick 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.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.How do the symptoms of this disease?TAY-SACHS DISEASEWhat 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 systemThe 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 ageJuvenile -symptoms typically appear between ages 2 and 5, but can occur anytime during childhoodLate Onset -symptoms typically appear in adolescence or early adulthood, but can appear later

19Tay-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 Hex-A, 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 beta-hexosaminidase 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.

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 GM2-gangliosidosis.Where is the disease started?

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 BlindnessDecreased muscle toneIncreased startle responseParalysis or loss of muscle functionSeizuresDelayed mental and social developmentSlow growthRed spot on the macula (an oval-shaped area near the center of the retina in the eye)

FABRY DISEASEWhat 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 skinFabry on legTHANK YOU