About lipid storage disease

What is lipid storage disease?

Chanarin Dorfman syndrome is a rare hereditary disorder of fat (lipid) metabolism. It is characterized by scaly skin (ichthyosis), degeneration of the muscles (myopathy), and abnormal white blood cells with small spaces (vacuoles) filled with fat (lipids).

What are the symptoms for lipid storage disease?

Lipid storage disease is a condition in which an enzyme in catabolism or transport of lipid is expressed in a lower quantity, or the expressed enzyme is non-functional. It leads to the accumulation of lipids in abnormally high quantities.

Symptoms

  • Lipid storage diseases are genetic disorders, and hence, the defects are present from birth. The age at which affected individuals develop symptoms and progression depends on the gene involved and the disease subtype.
  • The disease affects various organs, including the heart, kidney, liver, lungs, muscular and nervous system.
  • Cardiovascular impairments: atherosclerosis, heart enlargement, heart attack, Anemia,
  • Liver abnormalities: lesions, hepatomegaly, jaundice, splenomegaly
  • Neurological abnormalities: difficulty in walking and swallowing, progressive loss of hearing, dementia, burning pain in arms and legs, Lethargy, sleepiness, Seizures, cherry red spot in eye, cloudy vision, oculomotor disorders,
  • Muscular and skeletal: coarsening of facial features, muscle Weakness, distended abdomen, joint stiffness, muscular atrophy, hypertonia
  • Renal complications, and lymph node swelling.
  • The symptoms develop in characteristic combinations in different lipid storage diseases.


Conditions
Lack of muscle coordination,Brain degeneration,
Seizures,Loss of muscle tone,Learning problems,
spasticity,Feeding and swallowing difficulties,Slurred speech
Drugs
Enzyme replacement therapy (for Gaucher and Fabry diseases),Migalastat (Galafold),Antiplatelet drugs used to treat stroke helps slow down decline of kidney function seen in Fabry disease
Symptoms
Brain damage,Liver malfunction,Enlarged spleen and liver,Skeletal disorders and bone lesions that may cause pain and fractures,Distended abdomen,Swelling of lymph nodes and (occasionally) adjacent joints,A brownish tint to the skin,Anemia,Yellow spots in the eyes,Low blood platelets

What are the causes for lipid storage disease?

The impaired transport and storage of lipids, as well as disturbed structure and function of lipid membrane microdomains, are the causes of Lipid storage disorders. The disorders affect various organs and organ systems as the accumulated lipids restrain normal functioning.

There are various types of lipid storage diseases based on the specific transporter/enzyme involved. They are as follows:

  • Gaucher disease results from the mutation in the gene for the enzyme glucocerebrosidase that breaks glucocerebroside, a sphingolipid.
  • Niemann-Pick disease results from the mutations in the genes denoted by SMPD 1, NPC1, and NPC2. SPDM1 codes for acid sphingomyelinase that breaks the lipid sphingomyelin, whereas NPC1 and NPC2 code for lipid transporters.
  • Fabry disease results from the deficiency of alpha-galactosidase A, which breaks down the glycolipid called globotriaosylceramide.
  • Farber’s disease is caused by a deficiency of acid ceramidase that breaks fatty acids from ceramide lipids.
  • Gangliosidoses: GM1 gangliosidosis is caused by the deficiency of beta-galactosidase that leads to the accumulation of acidic lipids.
  • GM2 type is caused by the deficiency of hexosaminidase.
  • Krabbe disease is caused by the efficiency of the enzyme galactocerebrosidase
  • Metachromatic leukodystrophy occurs due to the deficiency of the enzyme arylsulfatase A.
  • Wolman’s disease is due to the deficiency of the enzyme acid lipase.


Conditions
Lack of muscle coordination,Brain degeneration,
seizures,Loss of muscle tone,Learning problems,
spasticity,Feeding and swallowing difficulties,Slurred speech
Drugs
Enzyme replacement therapy (for Gaucher and Fabry diseases),Migalastat (Galafold),Antiplatelet drugs used to treat stroke helps slow down decline of kidney function seen in Fabry disease
Symptoms
Brain damage,Liver malfunction,Enlarged spleen and liver,Skeletal disorders and bone lesions that may cause pain and fractures,Distended abdomen,Swelling of lymph nodes and (occasionally) adjacent joints,A brownish tint to the skin,Anemia,Yellow spots in the eyes,Low blood platelets

What are the treatments for lipid storage disease?

Lipid storage disease is a group of diseases by which abnormal amounts of lipids accumulate in the body. The diseases include Gaucher disease, Niemann pick disease, Fabry disease, Farber’s disease, Gangliosidosis, Krabbe disease, Metachromatic leukodystrophy, and Wolman’s disease.

Treatments:
There is no complete cure for any of the lipid storage diseases available. But the disease is managed with supportive and organ-specific treatments.

1. Enzyme-replacement therapy
The underlying mechanism of the diseases is the deficiency of specific enzymes. Enzyme replacement therapy involves the oral or intravenous administration of enzymes or the drugs or analogs that function as enzymes. FDA has approved a few therapies:
Sebelipase alfa: a recombinant form of acid lipase for Wolman’s disease, administered at the dose of 1mg/kg of body weight every week
Cerezyme, Velaglucerase alfa, and Taliglucerase alfa: function as glucocerebrosidase for Gaucher disease
Agalsidase alpha and agalsidase beta: recombinant forms of alpha-galactosidase A for Fabry disease

2. Pharmacological chaperones
These are molecules that assist protein folding. Migalastat, assist the folding of faulty alpha-galactosidase in patients with Fabry disease.

3. Hematopoietic stem cell transplantation
This approach is still in infancy, innovated only a few decades ago. It involves the intravenous infusion of blood stem line cells with the expression of the functional enzyme.

4. Drugs
Various drugs such as anti-inflammatory drugs, anti-epileptic, and hypolipidemic agents are available to treat symptoms.

Conditions
Lack of muscle coordination,Brain degeneration,
seizures,Loss of muscle tone,Learning problems,
spasticity,Feeding and swallowing difficulties,Slurred speech
Drugs
Enzyme replacement therapy (for Gaucher and Fabry diseases),Migalastat (Galafold),Antiplatelet drugs used to treat stroke helps slow down decline of kidney function seen in Fabry disease
Symptoms
Brain damage,Liver malfunction,Enlarged spleen and liver,Skeletal disorders and bone lesions that may cause pain and fractures,Distended abdomen,Swelling of lymph nodes and (occasionally) adjacent joints,A brownish tint to the skin,Anemia,Yellow spots in the eyes,Low blood platelets

What are the risk factors for lipid storage disease?

Lipid storage diseases are metabolic disorders caused by genetic mutations that reflect the under-expression of enzymes involved in lipid metabolism. It causes lipid accumulation in the liver, spleen, kidney, heart, nervous system, lymph nodes, and lungs. This accumulation interferes with respective physiological activities and affects the health and thus quality of life.

Risk factors:

  • Lipid storage diseases can be inherited in an autosomal recessive manner, except Fabry’s disease, which follows x-linked inheritance.
  • When both the parents are affected, their children are all affected; that is, the risk is highest.
  • X-linked inheritance of Fabry’s disease: Male children with affected mothers are born affected as they receive the affected gene through X-chromosome. When the mother is a carrier, the chances of inheritance are 50 percent for a male child.
  • Diet rich in lipids increase enhances the accumulation, and the condition progresses.
  • Habitual activities such as smoking, alcohol consumption, and drug abuse increase the risk of elevated symptoms, especially respiratory and cardiovascular complications.
  • Non-steroid anti-inflammatory drugs also increase the risk of renal complications.


Conditions
Lack of muscle coordination,Brain degeneration,
seizures,Loss of muscle tone,Learning problems,
spasticity,Feeding and swallowing difficulties,Slurred speech
Drugs
Enzyme replacement therapy (for Gaucher and Fabry diseases),Migalastat (Galafold),Antiplatelet drugs used to treat stroke helps slow down decline of kidney function seen in Fabry disease
Symptoms
Brain damage,Liver malfunction,Enlarged spleen and liver,Skeletal disorders and bone lesions that may cause pain and fractures,Distended abdomen,Swelling of lymph nodes and (occasionally) adjacent joints,A brownish tint to the skin,Anemia,Yellow spots in the eyes,Low blood platelets

Is there a cure/medications for lipid storage disease?

Lipid storage disease is a group of inborn metabolic errors caused by mutations in the gene that instruct the synthesis of lipid-metabolizing enzymes. The deficiency of enzymes decreases the catabolism of lipids. As a result, lipid accumulates in the tissues and blood. Commonly, lipids accumulate in the liver, heart, kidney, spleen, lymph nodes, and brain. However, in some types, lipids accumulate in the lungs, peripheral nerves, eyes, and joints.

Cure/medications:
There is no complete cure available.
There are ways to treat symptoms as follows:

  • The faulty enzymes are replaced by drug/enzyme analogs that can perform their functions. It is called Enzyme replacement therapy. FDA-approved enzyme replacements are:
  • Sebelipase alfa to treat Wolman’s disease
  • Cerezyme, Velaglucerase alfa, and Taliglucerase alfa for Gaucher disease
  • Agalsidase alpha, and Agalsidase beta for Fabry'S disease
  • Eliglustat and Miglustat are substrate-reducing agents that control lipid synthesis.
  • The non-functional enzymes can be assisted to fold into the active enzyme using pharmacological chaperones. Migalastat is one such drug used to treat Fabry’s disease.
  • Hematopoietic stem cell transplantation
  • Statins help maintain low lipid levels.
  • Physiotherapy to loosen joints and ease mobility.
  • Anti-epileptic drugs to control seizures.
  • Muscle relaxants to reduce spasms.


Conditions
Lack of muscle coordination,Brain degeneration,
seizures,Loss of muscle tone,Learning problems,
spasticity,Feeding and swallowing difficulties,Slurred speech
Drugs
Enzyme replacement therapy (for Gaucher and Fabry diseases),Migalastat (Galafold),Antiplatelet drugs used to treat stroke helps slow down decline of kidney function seen in Fabry disease
Symptoms
Brain damage,Liver malfunction,Enlarged spleen and liver,Skeletal disorders and bone lesions that may cause pain and fractures,Distended abdomen,Swelling of lymph nodes and (occasionally) adjacent joints,A brownish tint to the skin,Anemia,Yellow spots in the eyes,Low blood platelets

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