Lipidoses are genetic disorders, passed from parents to their children, characterized by defects of the digestive system that impair the way the body uses dietary fat. When the body is unable to properly digest fats, lipids accumulate in body tissues in abnormal amounts.


The digestion, storage, and use of fats (lipids) from foods are complex processes that involve hundreds of chemical reactions in the body. In most people, the body is already programmed by its genetic code to produce all of the enzymes and chemicals necessary to carry out these functions. These genetic instructions are passed from parents to their offspring.

People with lipidoses are born without the genetic codes needed to tell their bodies how to complete a particular part of the fat digestion and utilization process. In most of these disorders, the body does not produce a certain enzyme, or specialized chemical. Over 30 different disorders of fat metabolism are related to genetic defects. Some people can carry the gene for these defects, but be free of symptoms; although the defects are passed from parents to children, the parents often do not have the disorders themselves.

There is great variance in the symptoms, available treatments, and long-term consequences of these conditions. Some of the conditions become apparent shortly after the infant is born. In other lipid disorders, symptoms may not develop until adulthood. For most of the lipidoses, diagnosis is suspected based on symptoms and family history. Tests of blood, urine, and tissue can be used to confirm the diagnosis. Genetic testing can be used, in some cases, to identify the defective gene. Some of these disorders can be controlled with changes in the diet, medications, or enzyme supplements. However, for many of these diseases, no treatment is available. Some may cause death in childhood or contribute to a shortened life expectancy. This section focuses on some of the most common or most serious lipidoses.


Lipidoses are very rare. The number of people affected depends on the disease, but for many diseases incidence is as little as one in 40,000 people. Some diseases have a higher prevalence in specific populations.

Fabry's disease

Causes and symptoms

Approximately one in every 40,000 males is born with Fabry's disease. This condition has an X-linked, recessive pattern of inheritance, meaning that the defective gene is carried on the X chromosome. A female who carries a defective recessive gene on one of her two X chromosomes will not have the disease because she also has one good X chromosome. However, she has a 50 percent chance of passing the defective gene to her sons. The sons inheriting one defective gene will develop the disorder because a male has only one X chromosome, which he receives from his mother and one Y chromosome from his father. The mother also has a 50 percent chance of passing the defective recessive gene to her daughters who will be carriers of the disorder (like their mother), but will not show symptoms of the disease. Some female carriers of Fabry's disease show mild signs of the disorder, especially cloudiness of the cornea.

The gene that is defective in Fabry's disease causes a deficiency of the enzyme alpha-galactosidase A. Without this enzyme, fatty compounds start to line the blood vessels. The collection of fatty deposits eventually affects blood vessels in the skin, heart, kidneys, and nervous system. The first symptoms in childhood are pain and discomfort in the hands and feet brought on by exercise , fever , stress, or changes in the weather. A raised rash of dark red-purple spots is common, especially on skin between the waist and the knees. Other symptoms include a decreased ability to sweat and changes in the cornea or outer layer of the eye. Although the disease begins in childhood, it progresses very slowly. Kidney and heart problems develop in adulthood.


A diagnosis of Fabry's disease can be confirmed by a blood test to measure for alpha-galactosidase A. Women who are carriers of the defective gene can also be identified by a blood test.


Treatment focuses on prevention of symptoms and long-term complications. Daily doses of diphenylhydantoin (Dilantin) or carbamazapine (Tegretol) can prevent or reduce the severity of pain in the hands and feet associated with this condition. A diet low in sodium and protein may be beneficial to those individuals who have some kidney complications. If kidney problems progress, kidney dialysis or kidney transplantation may be required. Enzyme replacement therapy is being explored.


Although patients with Fabry's disease usually survive to adulthood, they are at increased risk for stroke , heart attack, and kidney damage.

Gaucher disease

Causes and symptoms

Gaucher (pronounced go-shay) disease is the most common of the lipid storage disorders. It is found in populations all over the world (20,000–40,000 people have a type of the disease), and it occurs with equal frequency in males and females. Gaucher disease has a recessive pattern of inheritance, meaning that a person must inherit a copy of the defective gene from both parents in order to have symptoms of the disease. The genetic defect causes a deficiency of the enzyme glucocerebrosidase that is responsible for breaking down a certain type of fat and releasing it from fat cells. These fat cells begin to crowd out healthy cells in the liver, spleen, bones, and nervous system. Symptoms of Gaucher disease can start in infancy, childhood, or adulthood.

Three types of Gaucher disease have been identified, but there are many variations in how symptoms develop. Type 1 is the most common and affects both children and adults. It occurs much more often in people of Eastern European and Russian Jewish (Ashkenazi) ancestry, affecting one out of every 450 live births in this population. The first signs of the disease include an enlarged liver and spleen, causing the abdomen to swell. Children with this condition may be shorter than normal. Other symptoms include tiredness, pain, bone deterioration, broken bones, anemia, and increased bruising. Type 2 Gaucher disease is more serious, beginning within the first few months after birth. Symptoms, which are similar to those in type 1, progress rapidly, but also include nervous system damage. Symptoms of type 3 Gaucher disease begin during early childhood with symptoms like type 1. Unlike type 2, the progress of the disease is slower, although it also includes nervous system damage.


Gaucher disease may be suspected, based on symptoms, and is confirmed with a blood test for levels of the deficient enzyme. Samples of tissue from an affected area may also confirm a diagnosis.


The symptoms of Gaucher disease can be stopped and even reversed by treatment with enzyme replacement injections. Two enzyme drugs available are alglucerase (Ceredase) and imiglucerase (Cerezyme). Other treatments address specific symptoms such as anemia, broken bones, or pain.


The pain and deformities associated with symptoms can make coping with this illness very challenging for individuals and families. With treatment and control of symptoms, people with type 1 Gaucher disease may lead fairly long and normal lives. Most infants with type 2 die before age two. Children with type 3 Gaucher disease may survive to adolescence and early adulthood.

Krabbe's disease

Causes and symptoms

Krabbe's disease is caused by a deficiency of the enzyme galactoside beta-galactosidase. It has a recessive pattern of inheritance and is believed to occur in one out of 40,000 births in the United States. This condition, which is also called globoid cell leukodystrophy or Krabbe leukodystrophy, is characterized by acute nervous system degeneration. It develops in early infancy with initial symptoms of irritability, vomiting , and episodes of partial unconsciousness. Symptoms progress rapidly to seizures, difficulty swallowing, blindness, deafness, mental retardation , and paralysis.


No treatment is available.


Children born with Krabbe's disease die in infancy.

Niemann-pick disease

Causes and symptoms

At least five different forms of Niemann-Pick disease (NPD) have been identified. The different types seem to be related to the activity level of the enzyme sphingomyelinase. In patients with types A and B NPD, there is a build-up of sphingomyelin in cells of the brain, liver, spleen, kidney, and lung. Type A is the most common form of NPD and the most serious, with death usually occurring by the age of 18 months. Symptoms develop within the first few months of life and include poor appetite, failure to grow, enlarged liver and spleen, and the appearance of cherry red spots in the retina of the eye. Type B develops in infancy or childhood with symptoms of mild liver or spleen enlargement and lung problems. Types C and D NPD are related to cholesterol transfer out of cells. Children with types C or D grow normally in early childhood, but eventually develop difficulty in walking and loss of muscle coordination. Ultimately, the nervous system becomes severely damaged and these patients die. Type C occurs in any population, while type D has been identified only in individuals from Nova Scotia, Canada.


Diagnosis is confirmed by analyzing a sample of tissue. Prenatal diagnosis of types A and B NPD can be done with amniocentesis or chorionic villi sampling.


Treatment consists of supportive care to deal with symptoms and the development of complications. Bone marrow transplantation is being investigated as a possible treatment. Low-cholesterol diets may be helpful for patients with types C and D.


Patients with type A NPD usually die within the first 18 months of life. Type B patients generally live to adulthood but suffer from significant liver and lung problems. With types C and D NPD, there is significant nervous system damage leading to severe muscle spasms , seizures, and eventually coma and death. Some patients with types C and D die in childhood, while less severely affected individuals may survive to adulthood.

Refsum's disease

Causes and symptoms

Refsum's disease has a recessive pattern of inheritance and affects populations from Northern Europe, particularly Scandinavians. It is due to a deficiency of phytanic acid hydroxylase, an enzyme that breaks down a fatty acid called phytanic acid. This condition affects the nervous system, eyes, bones, and skin. Symptoms, which usually appear by age 20, include vision problems (retinitis pigmentosa and rhythmic eye movements, or nystagmus ), loss of muscle coordination, loss of sense of smell (anosmia), pain, numbness , and elevated protein in the cerebrospinal fluid.


A diet free of phytanic acid (found in dairy products, tuna, cod, haddock, lamb, stewed beef, white bread, white rice, boiled potatoes, and egg yolk) can reduce some of the symptoms. Plasmapheresis—a process where whole blood is removed from the body, processed through a filtering system, and then returned to the body—may be used to filter phytanic acid from the blood.

Tay-Sachs disease

Causes and symptoms

Tay-Sachs disease (TSD) is a fatal condition caused by a deficiency of the enzyme hexosaminidase A (Hex-A). The defective gene that causes this disorder is found in roughly one in 250 people in the general population. However, certain populations have significantly higher rates of TSD. French-Canadians living near the St. Lawrence River and in the Cajun regions of Louisiana are at higher risk of having a child with TSD. The highest risk seems to be in people of Eastern European and Russian Jewish (Ashkenazi) descent. Tay-Sachs disease has a recessive pattern of inheritance, and approximately one in every 27 people of Jewish ancestry in the United States carries the TSD gene. Symptoms develop in infancy and are due to the accumulation of a fatty acid compound in the nervous system. Early symptoms include loss of vision and physical coordination, seizures, and mental retardation. Eventually, the child develops problems with breathing and swallowing. Blindness, paralysis, and death follow.


Carriers of the Tay-Sachs related gene can be identified with a blood test. Amniocentesis or chorionic villi sampling can be used to determine if the fetus has Tay-Sachs disease.


There is no treatment for Tay-Sachs disease. Parents who are identified as carriers may want to seek genetic counseling. If a fetus is identified as having TSD, parents can then consider their options.


Children born with Tay-Sachs disease become increasingly debilitated; most die by about age four.

Wolman's disease

Causes and symptoms

Wolman's disease is caused by a genetic defect with a recessive pattern of inheritance that results in a deficiency of an enzyme that breaks down cholesterol. This causes large amounts of fat to accumulate in body tissues. Symptoms begin in the first few weeks of life and include an enlarged liver and spleen, adrenal calcification (hardening of adrenal tissue due to deposits of calcium salts), and fatty stools.


No treatment is available.


Death generally occurs before six months of age.


There is no known way to prevent lipidoses. Couples who have family histories of genetic defects can undergo genetic testing and counseling to see if they are at risk for having a child with one of the lipidoses disorders. During pregnancy, cell samples can be collected from the fetus using amniocentesis or chorionic villi sampling. The results of these tests can indicate if the developing fetus has a lipidosis disorder.


Amniocentesis —A procedure performed at 16-18 weeks of pregnancy in which a needle is inserted through a woman's abdomen into her uterus to draw out a small sample of the amniotic fluid from around the baby for analysis. Either the fluid itself or cells from the fluid can be used for a variety of tests to obtain information about genetic disorders and other medical conditions in the fetus.

Chorionic villus sampling —A procedure performed at 10 to 12 weeks of pregnancy in which a needle is inserted either through the mother's vagina or abdominal wall into the placenta to withdraw a small amount of chorionic membrane from around the early embryo. The amniotic fluid can be examined for signs of chromosome abnormalities or other genetic diseases.

Lipids —Organic compounds not soluble in water, but soluble in fat solvents such as alcohol. Lipids are stored in the body as energy reserves and are also important components of cell membranes. Commonly known as fats.

Recessive —Refers to an inherited trait that is outwardly obvious only when two copies of the gene for that trait are present. An individual displaying a recessive trait must have inherited one copy of the defective gene from each parent.

X-linked —A gene carried on the X chromosome, one of the two sex chromosomes.

Parental concerns

Lipidoses have a variety of different symptoms and progressions. There are treatments for some—but not all—lipidoses. Treating the symptoms is always an integral part of lessening the impact of the disease. If parents have one child with a lipidoses disorder and are considering having other children, genetic counseling or in utero testing of the fetus may be beneficial.



Desnick, Robert J., and Michael M. Kaback, eds. Tay-Sachs Disease. San Diego, CA: Academic, 2001.

Vinken, Pierre J., and George W. Bruyn, eds. Neurodystrophies and Neurolipidoses. New York: Elsevier, 1996.


Enderlin, Carol, et al. "Gaucher Disease." American Journal of Nursing 103, no. 12 (December 2003): 50–62.

Futerman, Anthony H. et al. "New Directions in the Treatment of Gaucher Disease." Trends in Pharmacological Sciences 25, no. 3 (March 2004): 147–52.

Wilcox, William R., et al. "Long-term Safety and Efficacy of Enzyme Replacement Therapy for Fabry Disease." American Journal of Human Genetics 75, no. 1 (July 2004): 65–75.


National Organization for Rare Diseases. 55 Kenosia Avenue, PO Box 1968, Danbury, CT 06813-1968. (203) 744-0100 or 1-800-999-6673. Fax: (203) 798-2291. Web site:

Tish Davidson, A.M. Altha Roberts Edgren

User Contributions:

Comment about this article, ask questions, or add new information about this topic: