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Disorders of Lipid Metabolism

by Lee M. Sanders, MD, MPH

Fats (lipids) are an important source of energy for the body. The body’s store of fat is constantly broken down and reassembled to balance the body’s energy needs with the food available. Groups of specific enzymes help the body break down and process fats. Certain abnormalities in these enzymes can lead to the buildup of specific fatty substances that normally would have been broken down by the enzymes. Over time, accumulations of these substances can be harmful to many organs of the body. Disorders caused by the accumulation of lipids are called lipidoses. Other enzyme abnormalities prevent the body from converting fats into energy normally. These abnormalities are called fatty acid oxidation disorders.

Gaucher’s Disease

Gaucher’s disease is caused by a buildup of glucocerebrosides in tissues. Children who have the infantile form usually die within a year, but children and adults who develop the disease later in life may survive for many years.

In Gaucher’s disease, glucocerebrosides, which are a product of fat metabolism, accumulate in tissues. Gaucher’s disease is the most common lipidosis. The disease is most common among Ashkenazi (Eastern European) Jews. Gaucher’s disease leads to an enlarged liver and spleen and a brownish pigmentation of the skin. Accumulations of glucocerebrosides in the eyes cause yellow spots called pingueculae to appear. Accumulations in the bone marrow can cause pain and destroy bone.

Type 1 , the chronic form of Gaucher’s disease, is the most common. It results in an enlarged liver and spleen and bone abnormalities. Most commonly diagnosed during adulthood, type 1 Gaucher’s disease may lead to severe liver disease, including increased risk of bleeding from the stomach and esophagus and liver cancer. Neurologic problems can also occur.

Type 2 , the infantile form, usually causes death in the first year of life. Affected infants have an enlarged spleen and severe neurologic problems.

Type 3 , the juvenile form, can begin at any time during childhood. Children with type 3 disease have an enlarged liver and spleen, bone abnormalities, and slowly progressive neurologic problems. Children who survive to adolescence may live for many years.

Many people with Gaucher’s disease can be treated with enzyme replacement therapy, in which enzymes are given by vein, usually every 2 weeks. Enzyme replacement therapy is most effective for people who do not have nervous system complications.

Tay-Sachs Disease

Tay-Sachs disease is caused by a buildup of gangliosides in the tissues. This disease results in early death.

In Tay-Sachs disease, gangliosides, which are products of fat metabolism, accumulate in tissues. The disease is most common among families of Eastern European Jewish origin. At a very early age, children with this disease become progressively intellectually disabled and appear to have floppy muscle tone. Spasticity develops and is followed by paralysis, dementia, and blindness. These children usually die by age 3 or 4. The disease cannot be treated or cured.

Before conception, parents can find out whether they carry the gene that causes the disease. During pregnancy, Tay-Sachs disease can be identified in the fetus by chorionic villus sampling or amniocentesis.

Niemann-Pick Disease

Niemann-Pick disease is caused by a buildup of sphingomyelin or cholesterol in the tissues. This disease causes many neurologic problems.

In Niemann-Pick disease, the deficiency of a specific enzyme results in the accumulation of sphingomyelin (a product of fat metabolism) or cholesterol. Niemann-Pick disease has several forms, depending on the severity of the enzyme deficiency, which determines how much sphingomyelin or cholesterol accumulates. The most severe forms tend to occur in Jewish people. The milder forms occur in all ethnic groups.

In the most severe form (type A), children fail to grow normally and have several neurologic problems. These children usually die by age 3. Children with type B disease develop fatty growths in the skin, areas of dark pigmentation, and an enlarged liver, spleen, and lymph nodes. They may be intellectually disabled. Children with type C disease develop symptoms during childhood, with seizures and neurologic deterioration.

Some forms of Niemann-Pick disease can be diagnosed in the fetus by chorionic villus sampling or amniocentesis. After birth, the diagnosis can be made by a liver biopsy (removal of a tissue specimen for examination under a microscope). None of the types of Niemann-Pick disease can be cured, and children tend to die of infection or progressive dysfunction of the central nervous system. Currently, some therapies that may slow or halt the progression of symptoms in types B and C are being studied.

Fabry’s Disease

Fabry’s disease is caused by a buildup of glycolipid in tissues. This disease causes skin growths, pain in the extremities, poor vision, recurrent episodes of fever, and kidney or heart failure.

In Fabry’s disease, glycolipid, which is a product of fat metabolism, accumulates in tissues. Because the defective gene for this rare disorder is carried on the X chromosome, the full-blown disease occurs only in males (see see Inheritance Patterns : X-Linked Inheritance). The accumulation of glycolipid causes noncancerous (benign) skin growths (angiokeratomas) to form on the lower part of the trunk. The corneas become cloudy, resulting in poor vision. A burning pain may develop in the arms and legs, and children may have episodes of fever. Children with Fabry’s disease eventually develop kidney failure and heart disease, although most often, they live into adulthood. Kidney failure may lead to high blood pressure, which may result in stroke.

Fabry’s disease can be diagnosed in the fetus by chorionic villus sampling or amniocentesis. The disease cannot be cured or even treated directly, but researchers are investigating a treatment in which the deficient enzyme is replaced by transfusion. Treatment consists of taking analgesics to help relieve pain and fever or anticonvulsants. People with kidney failure may need a kidney transplant.

Did You Know...

  • Fabry’s disease affects only boys.

Fatty Acid Oxidation Disorders

Fatty acid oxidation disorders are caused by a lack or deficiency of the enzymes needed to break down fats, resulting in delayed mental and physical development.

Several enzymes help break down fats so that they may be turned into energy. An inherited defect or deficiency of one of these enzymes leaves the body short of energy and allows breakdown products, such as acyl-CoA, to accumulate. The enzyme most commonly deficient is medium chain acyl-CoA dehydrogenase (MCAD). Other enzyme deficiencies include short chain acyl-CoA-dehydrogenase deficiency (SCAD), long chain-3-hydroxyacyl-CoA-deficiency (LCHAD), and trifunctional protein deficiency (TFP).

MCAD Deficiency

This disorder is one of the most common inherited disorders of metabolism, particularly among people of Northern European descent.

Symptoms usually develop between birth and age 3. Children are most likely to develop symptoms if they go without food for a period of time (which depletes other sources of energy) or have an increased need for calories because of exercise or illness. The level of sugar in the blood drops significantly, causing confusion or coma. Children become weak and may have vomiting or seizures. Over the long term, children have delayed mental and physical development, an enlarged liver, heart muscle weakness, and an irregular heartbeat. Sudden death may occur.

Since 2007, nearly every state in the United States has required that all newborns be screened for MCAD with a blood test. Immediate treatment is with glucose given by vein. For long-term treatment, children must eat often, never skip meals, and consume a diet high in carbohydrates and low in fats. Supplements of the amino acid carnitine may be helpful. The long-term outcome is generally good.


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