Information on the following diseases can be found in the Related Disorders section of this report:

• Diencephalic Syndrome
• Cushing Syndrome
• Multiple Symmetric Lipomatosis
• Congenital Adrenal Hyperplasia

Lipodystrophies may affect a small area of the body, a large part of the body, or the entire body.

Extreme decreases of fat tissue over the entire body (Total Lipodystrophy) may be inherited or acquired. The inherited form is present at birth (congenital) and is characterized by marked absence of fat tissue in the face, trunk and limbs with prominent muscles. The acquired form usually begins during childhood or adulthood with loss of fatty tissue also noticeable in the face, trunk, and limbs. Congenital generalized Lipodystrophy is another inherited form of Lipodystrophy present at birth which is characterized by generalized absence of fat tissue under the skin, but without prominent muscles. Abnormal carbohydrate and lipid metabolism occur in both the inherited and the acquired forms.

Leprechaunism is a rare inherited form of Total Lipodystrophy that includes characteristic facial features, growth retardation before birth, enlargement of sex organs, marked deficiency of fatty tissue under the skin, and other skin abnormalities. Metabolic problems can occur, and many affected infants exhibit extreme failure to thrive. (For more information on Leprechaunism, please choose "Leprechaun" as your search term in the Rare Disease Database.)

Other symptoms of Total Lipodystrophies may include prominent-appearing muscles due to the lack of fat tissue under the skin, jaw muscles that appear to stand out, sunken cheeks, and a wrinkled forehead. The bones and muscles may be clearly outlined, and the abdomen is often distended. Skeletal growth and maturation appear to be accelerated in some cases. Mild to moderate high blood pressure may occur, and the liver tends to become enlarged (hepatomegaly). In some cases, metabolic abnormalities may not develop until Diabetes Mellitus first appears, usually after the onset of puberty. Excessive fatty acids in the blood (hyperlipidemia), and over-production of body heat (hypermetabolism) may then occur.

The following conditions may be associated with forms of Total Lipodystrophy: Acanthosis Nigricans (a skin disorder characterized by gray or black darkening and thickening of the skin which occurs frequently in Lipodystrophy patients around the onset of puberty), Acromegaly (gigantism), excessive hair growth (hirsutism or hypertrichosis), eruptive yellowish spots on the skin, and thickened skin. Generalized hyperpigmentation, liver disease, central nervous system disorders, an enlarged heart, and enlargement of external genitalia may also develop. Mental retardation has been associated with a few cases of Lipodystrophy. (For more information on any of the above mentioned disorders or conditions, choose the appropriate name as your search term in the Rare Disease Database).

Partial Lipodystrophy may be either inherited or acquired and is usually marked by the absence of fat tissue under the skin. Facial involvement, and wasting (atrophy) of the extremities or the trunk may or may not occur. The acquired form of partial Lipodystrophy is the most common form of Lipodystrophy, and is also known as "cephalothoracic progressive lipodystrophy". This condition is often progressive and may occur on only one side of the body. It has been associated with kidney disease, Diabetes Mellitus, hyperpigmentation, excessive hairiness (hirsutism), an enlarged liver, and the presence of excessive amounts of fatty acids in the blood (hyperlipemia). A cold sensation in involved areas, vague abdominal complaints or vomiting, frequent diarrhea, headaches, nervousness and fatigue are the major symptoms of Partial Lipodystrophy. A rapid heartbeat, lack of nerve conduction in fingers or toes resulting in tingling and/or coldness (Raynaud's phenomenon), and excessive sweating may also occur.

Various conditions are associated with Partial Lipodystrophy including central nervous system dysfunction, Hyperthyroidism, Diabetes Mellitus, menstrual disorders, ovarian abnormalities, and underdevelopment of sex organs (hypogonadism). Liver enlargement and kidney dysfunction (which is more serious) have been observed in some patients. Loss of protein through the urine occurs more frequently in Partial Lipodystrophy than in other forms of Lipodystrophy. (For more information on Diabetes Mellitus, or any other disorders or conditions mentioned above, choose the appropriate name as your search term in the Rare Disease Database).

When Partial Lipodystrophy occurs in conjunction with Diabetes Mellitus (Lipoatrophic Diabetes), it can be either inherited or acquired, and generalized or partial. The acquired form may begin during childhood or adulthood and may involve part of the body or the entire body. It often develops following an acute illness, but may arise without warning. Both the congenital and acquired forms are associated with abnormalities in carbohydrate metabolism, which can be manifested by low blood sugar (hypoglycemia), excessive loss of glucose through the urine (glucosuria), increased plasma insulin levels, and insulin resistance. The inherited form is characterized by fat atrophy of the limbs and trunk without involvement of the face and neck. The disorder usually begins at puberty but may not appear until middle age.

Other conditions which may be associated with Lipoatrophic Diabetes include insulin resistance, high blood sugar (hyperglycemia), severely elevated levels of triglycerides in the blood (hypertriglyceridemia) and eruptive yellow nodules or plaques on the skin (xanthomas). In affected females, the vaginal labia are enlarged, and the ovaries tend to develop cysts. Acanthosis Nigricans (a skin disorder characterized by gray or black darkening and thickening of the skin which occurs frequently in Lipodystrophy patients around the onset of puberty), is usually present. Kidney and liver disease usually do not occur.

Acquired Lipoatrophic Diabetes usually begins during adolescence or early adulthood. It resembles congenital Total Lipodystrophy due to the occurrence of Acanthosis Nigricans, excessive amounts of lipid in the blood (hyperlipidemia), and liver-spleen enlargement (hepatosplenomegaly) which may be due to cirrhosis of the liver. Insulin-resistant Diabetes Mellitus is almost always present, but neurologic, heart, and kidney abnormalities are usually absent.

Partial Lipodystrophy associated with developmental abnormalities is inherited, non-progressive and involves the face and buttocks. It begins during infancy or early childhood, and is associated with vision problems (Rieger's Anomaly), short stature, underdevelopment of the midface, lack of normal hair growth on the scalp (hypotrichosis), and insulin-deficient Diabetes. Tooth abnormalities also occur.

Localized Lipodystrophies have easily identifiable, multiple lesions often associated with inflammation of part of the abdominal wall (lymphocytic panniculitis).

Mesenteric Lipodystrophy is a form of localized Lipodystrophy involving fat deposits in lymph nodes near the small intestines. It is also known as "mesenteric panniculitis", "lipogranuloma of the mesentery" or Whipple's Disease. (For more information on this disorder, choose "Whipple" as your search term in the Rare Disease Database.)

Membranous Lipodystrophy is an inherited, localized lipodystrophy characterized by multiple cystic bone lesions on both sides of the body. Progressive neuropsychiatric symptoms including dementia, seizures, lack of muscle coordination (ataxia), tremors, and loss of consciousness may also occur. Additionally, the lens of the eyes may be involved.

Centrifugal Lipodystrophy is a rare localized condition characterized by a small skin depression enlarging in a circular pattern. The depression is due to a marked wasting of fatty tissue just under the skin. Localized Lipodystrophies are usually characterized as small, well-defined points of wasting (atrophy) with or without other associated diseases.

Total Lipodystrophy is inherited as a recessive trait. The exact cause of Partial Lipodystrophy is not known, although researchers believe it may be either inherited, infectious, an immune system abnormality, or originating within nerve tissue (neurogenic dysfunction). It may also be associated with other disorders as a symptom. Lipoatrophic Diabetes may be either inherited as an autosomal recessive trait, or acquired. Localized Lipodystrophies are thought to be caused by inflammation of affected tissue. Mesenteric Lipodystrophy (Whipple's Disease) is thought to be caused by fat deposits in lymph nodes near the small intestine. (For more information on Whipple Disease, choose "Whipple" as your search term in the Rare Disease Database.) Membranous Lipodystrophy is inherited by an unknown mode of transmission. Centrifugal Lipodystrophy is caused by wasting in the fat tissue just under the skin for unknown reasons.

Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

All of the Lipodystrophies are rare disorders affecting more females than males.

Symptoms of the following disorders can be similar to those of Lipodystrophy. Comparisons may be useful for a differential diagnosis:

Diencephalic Syndrome begins during infancy and is characterized by profound emaciation after initial normal growth, hyperactivity, and euphoria. Skin pallor, low blood pressure, and low blood sugar levels are present. This disorder is usually caused by a brain tumor.

Cushing Syndrome consists of a group of symptoms attributable to an excess of cortisol and certain other hormones from the cortex of the adrenal gland. It is usually caused by hormone secreting tumors of either the adrenal gland or the pituitary gland, or a hyperfunctioning pituitary gland. Sometimes hormone secreting tumors may develop in other organs. Cushing Syndrome occurs more frequently in females than in males, particularly women in their thirties, following a pregnancy. The prognosis is good if the causative tumors can be removed and/or drug therapy suppresses adrenal corticosteroid production. (For more information on this disorder, choose "Cushing" as your search term in the Rare Disease Database.)

Congenital Adrenal Hyperplasia (CAH) is a group of disorders resulting from defective synthesis of the corticosteroid hormones of the adrenal gland. The adrenal gland becomes enlarged because it tries to produce more and more of the hormones to compensate for their lack of effectiveness. The adrenal gland produces "male" sex hormones (androgens) in both males and females; because these are overproduced in certain forms of CAH, the external genitalia of some females with this disorder are masculinized to various degrees. Lack of glucocorticoids, especially cortisol, causes various kinds of metabolic problems. Lack of mineralocorticoids, primarily aldosterone, causes salt and water imbalances. In some cases, this can be fatal. (For more information on this disorder, choose "Adrenal Hyperplasia" as your search term in the Rare Disease Database.)

There is no known specific drug treatment for the Lipodystrophies. Long-term use of the dopamine receptor blocking drug Pimozide has not been effective. Diet therapy has been shown to be of some value in the control of metabolic problems. The use of small, frequent feedings and partial substitution of medium-chain triglycerides for polyunsaturated fats appears to be beneficial. Plastic surgery with implants of monolithic silicon rubber for correction of the deficient soft tissue of the face has been shown to be effective. False teeth may be useful in some cases for cosmetic reasons. Long-term treatment usually involves therapy for kidney and endocrine dysfunction.

If the patient has a genetic form of Lipodystrophy, genetic counseling will be of benefit for patients and their families. Other treatment is symptomatic and supportive.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

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ULTRASTRUCTURAL ABNORMALITIES OF THE LIVER IN TOTAL LIPODYSTROPHY: A. Klar, et al.; Arch Pathol Lab Med (February 1987, issue 111(2)). Pp. 197-199.

FAMILIAL PARTIAL LIPODYSTROPHY: TWO TYPES OF AN X LINKED DOMINANT SYNDROME, LETHAL IN THE HEMIZYGOUS STATE: J. Kobberling, et al.; J Med Genet (April 1986, issue 23(2)). Pp. 120-127.

LIPOLYSIS: PITFALLS AND PROBLEMS IN A SERIES OF 1,246 PROCEDURES: S. Cohen; Aesthetic Plast Surg (1985, issue 9(3)). Pp. 209-214.

MEMBRANOUS LIPODYSTROPHY (NASU DISEASE): CLINICAL AND NEUROPATHOLOGICAL STUDY OF A CASE: M. Minagawa, et al.; Clin Neuropathol (Jan-Feb 1985, issue 4(1)). Pp. 38-45.