Diseases & Conditions
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 result in the body being unable to properly convert fats into energy. These abnormalities are called fatty acid oxidation disorders.
Other Rare Hereditary Disorders of Lipid Metabolism
Wolman's disease is a disorder that results when specific types of cholesterol and glycerides accumulate in tissues. This disease causes enlargement of the spleen and liver. Calcium deposits in the adrenal glands cause them to harden, and fatty diarrhea (steatorrhea) also occurs. Infants with Wolman's disease usually die by 6 months of age.
Cerebrotendinous xanthomatosis occurs when cholestanol, a product of cholesterol metabolism, accumulates in tissues. This disease eventually leads to uncoordinated movements, dementia, cataracts, and fatty growths (xanthomas) on tendons. The disabling symptoms often appear after age 30. If started early, the drug chenodiol helps prevent progression of the disease, but it cannot undo any damage already done.
In sitosterolemia, fats from fruits and vegetables accumulate in blood and tissues. The buildup of fats leads to atherosclerosis, abnormal red blood cells, and fatty deposits on tendons (xanthomas). Treatment consists of reducing the intake of foods that are rich in plant fats, such as vegetable oils, and taking cholestyramine Some Trade Names QUESTRAN resin.
In Refsum's disease, phytanic acid, which is a product of fat metabolism, accumulates in tissues. A buildup of phytanic acid leads to nerve and retinal damage, spastic movements, and changes in the bone and skin. Treatment involves avoiding eating green fruits and vegetables that contain chlorophyll. Plasmapheresis, in which phytanic acid is removed from the blood, may be helpful.
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 in 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.
Most people who have Gaucher's disease develop type 1, the chronic form, which results in an enlarged liver and spleen and bone abnormalities. Most are adults, but children also may have type 1. Type 2, the infantile form, develops in infancy; infants with the disease have an enlarged spleen and severe nervous system abnormalities and usually die within a year. Type 3, the juvenile form, can begin at any time during childhood. Children with the disease have an enlarged liver and spleen, bone abnormalities, and slowly progressive nervous system abnormalities. 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 intravenously, usually every 2 weeks. Enzyme replacement therapy is most effective for people who do not have nervous system complications.
In Tay-Sachs disease, gangliosides, which are products of fat metabolism, accumulate in tissues. The disease is most common in families of Eastern European Jewish origin. At a very early age, children with this disease become progressively retarded 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. Tay-Sachs disease can be identified in the fetus by chorionic villus sampling or amniocentesis. The disease cannot be treated or cured.
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 and thus accumulation of sphingomyelin or cholesterol. 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 properly and have multiple 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 mentally retarded. Children with type C disease develop symptoms in 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.
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 Genetics: Replication ). The accumulation of glycolipid causes noncancerous skin growths (angiokeratomas) to form over 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 the person may have episodes of fever. People 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. People with kidney failure may need a kidney transplant.
Fatty Acid Oxidation Disorders
Several enzymes help break fats down 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). MCAD deficiency is one of the most common inherited disorders of metabolism, particularly in 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. The child becomes 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.
Some states screen newborns for MCAD deficiency with a blood test. Immediate treatment is with intravenous glucose. For long-term treatment, the child must eat often, never skipping 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.
Last full review/revision February 2003
Source: The Merck Manual Home Edition