Lysosomal Storage Disorders
Lysosomal Storage Disorders

What is Lysosomal Storage Disorders?

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What is Lysosomal Storage Disorders?

Lysosomal Storage Disorders (LSD) is a disease caused by the loss of the enzyme in the lysosomal. It causes certain compounds in the cells can not be digested or only partially digested. Compounds that are not digested it will accumulate and cause cell dysfunction and damage the health of the patient.

Lysosomal are organelles man who serves as the digestion in the cell. In the digestive tract, lysosomal containing the enzyme hydrolysis is used to break down food into cells. Digestive enzymes in the lysosomal to function optimally in acid so that the liquid in the lysosomal generally has a pH of acid. In addition to the digestion of food in the cells, the lysosomal also play a role in recycling cell organelle called the process of autophagy. If there are cell organelles damaged, lysosomal to destroy and digest organelles were constituent organelles would be used again by the cells for a variety of purposes.

Different types of LSD are caused by genetic disorders inherited from their parents. If a person suffers from an LSD, then that person is a carrier of the LSD type.

More than 50 LSD diseases have been identified. The symptoms and risk factors for LSD disease are different for each type of missing enzyme.

Types of Lysosomal Storage Disorders

Several types of LSD diseases that are common and successfully identified include:

  • Fabry’s disease. Fabry disease occurs because the patient can not produce alpha-galactosidase A enzyme that serves to digest fat. Fabry disease can also occur if a person has alpha-galactosidase A but not function properly. Fat that is not digested by the cells will accumulate in the body and cause constriction of blood vessels, damaging the skin, kidneys, heart, and nervous system.
  • Gaucher’s disease. Gaucher disease occurs due to a person experiencing a lack of glucoserebrosidase (GBA) enzyme that serves to digest fat called glucoserebroside. In people with Gaucher disease, this type of fat will accumulate in the spleen, liver, and bone marrow. Gaucher’s disease has 3 types.
    Type 1 is the most common type of Gaucher disease and does not invade the central nervous system. Gaucher type 1 disease can occur at any age, but generally occurs in the age of preteens and adolescents. Gaucher disease types 2 and 3 can attack the central nervous system and is more dangerous than Gaucher type 1 disease. Infants with Gaucher type 2 disease are rarely surviving by 2 years of age. Gaucher disease type 3 has the same symptoms as type 2, but appears at the age of preteens.
  • Krabbe’s disease. Krabbe disease results from a person experiencing a deficiency of the galactosilepamamidase enzyme. This enzyme serves to keep the myelin sheath on nerve cells that serve as a protector of nerve cells.
  • Niemann-Pick Disease. Patients with Niemann-Pick disease will experience fat metabolism disorder that causes the buildup of harmful compounds of fat in the body in various organs. Commonly affected organs are the liver, spleen, brain and bone marrow. Niemann-pick disease is divided into several groups, namely:

Group A and B that lack enzyme acid sphingomyelinase (ASM) which digest the compound of sphingomylein contained in various cells.

Group C that can not digest cholesterol and fat in the cells to accumulate in the brain, liver and spleen.

  • Methromromatic leukodystrophy (MLD). MLD disease occurs due to cell deficiency of arylsulfatase A enzyme that serves to digest fatty acid sulphate group. If not digested, sulfatide fat will accumulate in the white matter in the neural network and damage the nerve myelin sheath.
  • Mukopolosacaridosis (MPS). MPS is a disease that occurs due to the body has interference with enzymes that digest mucopolysaccharide. If mucopolysaccharide digestion is impaired due to enzymatic disturbance, it will produce heparan sulfate compounds, dermatan sulphate, and sulfate accumulation accumulating in the body.
  • Pompe’s disease. Pompe’s disease is caused by cells that are unable to digest complex sugars, such as glycogen, into simple sugars for cell energy sources. The impaired enzyme in Pompe’s disease is the alpha-glucosidase enzyme.
  • Tay-Sachs disease. The disease is caused by a deficiency of hexosaminidase A (Hex-A) enzyme that serves to digest the GM2 gangliosid fat compound in brain cells. Without the enzyme Hex-A, the fat compounds will accumulate and damage brain cells.

Causes of Lysosomal Storage Disorders

LSD disease is a genetic disease. Most of these diseases occur because recessive genes are inherited from both parents. If only one parent possesses the gene, then the born child will be the carrier.

LSD disease is a very rare disease. However there are several types of LSD that tend to appear on certain races. Examples are Tay-Sachs and Gaucher’s disease which is quite common in Jewish descent in Europe.

Symptoms of Lysosomal Storage Disorders

Every LSD disease has different symptoms. To ensure the disease is specific, further diagnosis is required in addition to observing the symptoms that appear.

The symptoms of Fabry’s disease generally are as follows:

  • Pain and burning sensation on the hands and feet. Pain that feels worse if the patient doing sports or experiencing fatigue.
  • Red and small spots appear in the area between the navel and the knee.
  • Blurred vision.
  • Hearing loss and ringing ears.
  • Less sweaty.
  • Abdominal and abdominal pain, especially after eating.
  • In men, symptoms that appear can worsen such as kidney failure, heart attack, hypertension, heart enlargement, and osteoporosis

Symptoms of Gaucher’s disease appear to be different according to the type. Symptoms of Gaucher type 1 disease are:

  • Easy bruising.
  • Nosebleed.
  • Fatigue.
  • Enlargement of the spleen and liver, which is characterized by enlargement of the abdomen.
  • Bone problems, such as pain, fractures, or arthritis.

Symptoms of Gaucher disease types 2 and 3 that generally appear are:

  • Slow eye movement.
  • Growth and slow development.
  • Spreads sound like a flute when breathing.
  • Seizures.
  • Brain damage and spinal cord.
  • Enlargement of the spleen and liver.

In perinatal Gaucher disease, which is the most severe Gaucher disease, most infants will not live for more than a few days. Symptoms are as follows:

  • The buildup of fluid in the baby’s body after birth.
  • Dry and scaly skin.
  • Enlargement of the spleen and liver.
  • Severe damage to the brain and spinal cord.

Symptoms of Krabbe disease can occur for a lifetime. In the first few months of the onset of these symptoms, the person may experience:

  • Muscle weakness.
  • Stiff on the legs.
  • Difficult to walk.
  • Hearing and vision loss.
  • Muscle cramp.
  • Seizures.

Symptoms of niemann-pick disease vary by group, both A, B and C. However, in general, people with niemann-pick disease will experience the following symptoms:

  • Enlargement of the spleen and liver.
  • Difficulty moving the eyeballs up and down.
  • Experiencing yellowish skin and eyes.
  • Growing growth barriers.
  • Hard to breathe.
  • Have heart problems.

Symptoms of methotromatic leukodystrophy (MLD) may appear differently by type. However, MLD symptoms that generally occur are as follows:

  • Numbness in the feet and hands.
  • Seizures.
  • Difficult to walk and talk.
  • Hearing and vision loss.

Symptoms of mucopolysaccharidosis (MPS) in general are:

  • Short body.
  • The joints are stiff.
  • Difficult to speak and hear.
  • Itchy nose constantly.
  • It’s hard to catch a lesson.
  • Heart disorders.
  • Joint pain.
  • Hard to breathe.
  • Depression.

The symptoms of Pompe’s disease are as follows:

  • Muscles weaken quite badly.
  • Bad muscle shape.
  • Slow growth and development in infants and children.
  • Enlargement of heart, liver, or tongue.

The symptoms of Tay-Sachs disease are easily observed in patients, especially in infants, is a movement disorder due to loss of control over the muscles. After that, the baby will have difficulty sitting, crawling, and walking due to late growth. Other symptoms are:

  • Red spots on the back of the eye.
  • Hearing and vision loss.
  • Seizures.

Diagnosis of Lysosomal Storage Disorders

The methods commonly used for LSD diagnosis are:

  • Prenatal and perinatal genetic testing. If one or both of the parents are suspected carriers of the LSD disease gene, then to predict whether the child has LSD disease, a genetic test can be performed. Genetic testing serves to map the genetic of the child and predict whether any enzyme is lost or damaged.
  • MRI. MRI is a diagnostic method that can see images of internal organs of the body to detect limb abnormalities due to LSD disease.
  • Biopsy. A biopsy is performed by taking a tissue sample then viewed under a microscope. Biopsy may show abnormal tissue structures due to lysosomal abnormalities.
  • Examination of oligosaccharide urine. This examination aims to detect oligosaccharide compounds that accumulate in the urine due to undigested by lysosomal enzymes. Some types of LSD disease that can be diagnosed using this method include gangliosidosis, galaktosialidosis, fruktosilaidosis, and aspartiglikosaminuria.
  • Glycosaminoglycan urine test (GAG). GAG detection methods are commonly used to diagnose whether a person is suffering from mucopolysaccharidosis. GAG is detected by purification, precipitation, and urinary centrifugation followed by colorimetric tests.
  • Detection of specific substrate. This examination is performed by detecting specific compounds that accumulate due to undigested by lysosomal. Compounds such as glycosphingolipids and oligosaccharides are almost always detectable in patients with LSD disease.
  • Examination of enzyme activity. Lysosomal enzymes were detected by flurometric analysis of fibroblast, leukocyte and serum cells. In patients with LSD, the enzyme activity tested will show very low levels or even undetectable. This method is used to detect common LSD diseases such as Fabry’s disease, Gaucher’s disease, Neimann-Pick’s disease, Krabbe’s disease, and Pompe’s disease.

If LSD disease can be detected early, treatment can help slow the progression of the disease and improve the prognosis of patients with the disease.

Treatment of Lysosomal Storage Disorders

Keep in mind that as one of the genetic diseases, LSD can not be cured. However, some methods of treatment can help patients to improve the quality of life, as well as slow the development of disease in patients. Some methods of treatment that can be given to patients are:

  • Enzyme replacement therapy. The goal of enzyme therapy is to give the lysosome enzyme lost or damaged to the patient. Enzymes may be administered intravenously so that the enzymatic function of the lysosome can remain well. This intravenous enzyme replacement therapy can not treat neural tissue disorders caused by LSD disease, but can minimize the disruption of body function due to loss of lysosomal enzymes in other tissues. Patients with Fabry’s disease and Gaucher’s disease can be treated using this method.
  • Substrate reduction therapy. The goal of this therapy is to reduce production and directly reduce the buildup of substrate compounds that need to be digested by lysosomal that are lost or damaged. An example of this type of therapy is therapy to reduce the production of glycosphlycolipid (GSL) by inhibiting GSL production in the body. This therapy can be used for people with Fabry disease, Niemann-Pick, and Gaucher.
  • Stem cell therapy. The goal of this therapy is to replace cells that lose the lysosomal enzyme by using healthy cells from the donor.
  • Enzyme stabilization therapy. This therapy aims to overcome LSD disease caused by the instability of certain enzymes. In some cases of LSD, the problematic enzyme is not caused by loss due to a mutation of the gene, but is impaired in its production process, so even if the enzyme is produced, it is not working properly.

In addition, there are also other handling to reduce the symptoms that appear. Among others are:

  • Provision of drugs
  • Surgery.
  • Physical therapy.
  • Wash the blood (hemodialysis).

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