Lipodystrophy

What is Lipodystrophy?

Lipodystrophy is a rare medical condition characterized by the abnormal or complete loss of body fat in certain areas or throughout the body. This fat loss can be present from birth or develop later in life and is often associated with metabolic problems such as insulin resistance, diabetes, and abnormal lipid levels.

There are several forms of lipodystrophy, which can be acquired (induced by another condition) or hereditary (caused by a genetic mutation).

Each form of lipodystrophy affects individuals differently and manifests in a variety of ways.

Function of adipose tissue

Adipose tissue, sometimes known as fat tissue, is found throughout your body, including under your skin and surrounding your internal organs. Adipose tissue performs a variety of vital tasks, such as:

• Storing energy-producing calories.
• Provide cushioning to different bodily areas.
• Supplying insulation, which keeps your body warm.
• Releasing certain hormones, such as leptin.
• Reducing inflammation.

Lipodystrophy-related body fat loss and/or redistribution can significantly alter your look, but it also interferes with several vital metabolic processes. Diabetes and abnormal cholesterol levels are common in lipodystrophy patients.

Types of lipodystrophy

Lipodystrophy may be classified into two major categories: acquired and genetic.

Genetic forms of lipodystrophy

The following are the hereditary types of lipodystrophy:

• Congenital generalized lipodystrophy (CGL): Berardinelli-Seip syndrome, another name for congenital generalized lipodystrophy, is an uncommon form of lipodystrophy characterized by substantial and occasionally nearly complete fat loss. You are born with a genetic mutation (change) that causes this disease. Usually, a diagnosis is made during the first year of life.
• FPLD, or familial partial lipodystrophy: Another genetic condition that is inherited is familial partial lipodystrophy. Later in a child’s life, it is frequently diagnosed. A child’s arms and legs are primarily affected by fat loss, with more fat in the face and neck.

Acquired lipodystrophy types

The following lipodystrophy types are acquired:

• Acquired generalized lipodystrophy (AGL):  Typically, acquired generalized lipodystrophy, also known as Lawrence syndrome, causes fat loss in the arms, legs, neck, and face. AGL-related fat loss might happen gradually over several months or even years, or quickly over a few weeks. It usually develops in childhood or adolescence, but it can happen at any age. AGL may have several causes.
• APL, or acquired partial lipodystrophy: The mark of acquired partial lipodystrophy, also known as Barraquer-Simons syndrome, is a progressive decrease of facial, neck, arm, and chest fat during childhood. Some APL patients may have extra fat on their legs, buttocks, or abdomen. Autoimmune diseases are frequently linked to APL.
• High active antiretroviral therapy (HAART) induced lipodystrophy (LD-HIV): After undergoing antiretroviral medication known as HIV-1 protease inhibitor-containing HAART, individuals with HIV develop this type of lipodystrophy. The length and intensity of treatment have an impact on the development of lipodystrophy. Most LD-HIV patients gradually lose fat in their faces, arms, and legs. Some people may gain extra fat in their waist, upper back, neck, and face.
• Localized lipodystrophy: This type of lipodystrophy simply causes fat loss in a small area of your body. It could happen at a common injection location for drugs (like insulin). The surrounding skin is often unaffected by localized lipodystrophy, which appears as a dimple or crater.

What is the difference between lipoatrophy and lipodystrophy?

Abnormal fat distribution is referred to as lipodystrophy. Fat loss, or lipoatrophy, is a part of it. To refer to the same disease, some scientists and medical professionals use both of these terms.

Who is affected by lipodystrophy?

Although acquired types of lipodystrophy can develop in adults, the majority of lipodystrophy cases start in children.

Except for lipodystrophy caused by highly active antiretroviral therapy (HAART) (LD-HIV), acquired types of lipodystrophy are more common in women. LD-HIV is more common in men, just as HIV is more common in men.

How common is lipodystrophy?

Although lipodystrophy diseases are generally uncommon, acquired (formed later in life) types of lipodystrophy have increased in frequency as a result of drug side effects.

What is the physical impact of lipodystrophy?

The effects of lipodystrophy vary depending on the type. Loss of adipose tissue and a deficiency in the hormone leptin are the two primary features of lipodystrophy that usually affect those who have the disorder.

The impact of losing adipose tissue on your body

Adipocytes are cells that make up adipose tissue, or body fat. A lipid droplet makes up around 90% of the cell volume in each adipocyte. Triglycerides, or fats, are stored in an adipocyte’s lipid droplet. Adipose tissue is harmed by lipodystrophy, which prevents healthy fat storage.

When you have lipodystrophy, your body may incorrectly store the fat you lose from your adipose tissue in other parts of your body, like your pancreas, liver, or skeletal muscle. This may result in several health issues, such as:

• Hepatic steatosis, or fatty liver disease.
• Hyperinsulinemia, or elevated insulin levels, and insulin resistance.
• diabetes.
• High amounts of triglycerides are known as hypertriglyceridemia.
• pancreatitis.
• metabolic syndrome.
• coronary artery disease.

These disorders won’t affect everyone with lipodystrophy, and others may experience more severe or moderate forms.

Leptin deficiency’s impact on your body

Loss of adipose tissue, or body fat, causes a deficiency in several hormones, especially leptin, in lipodystrophy patients.

Your adipose tissue releases a hormone called leptin, which aids your body in sustaining your ideal weight over time. It accomplishes this by controlling appetite by giving the impression of fullness. Leptin is still being researched, and scientists think it also has an impact on immune system function, endocrine system regulation, and metabolism.

Leptin levels are frequently lowered in lipodystrophy patients, which can lead to severe hunger, insulin resistance, and other medical issues.

Symptoms of lipodystrophy

Lipodystrophy has a wide range of symptoms due to its several varieties.

The most prevalent sign of lipodystrophy is a visible and gradually decreasing amount of fat in some body parts with normal or somewhat excessive levels of fat in other body parts.

For example, during childhood, patients with acquired partial lipodystrophy (APL) usually experience a slow loss of fat in their arms, chest, neck, and face. Some APL patients may have extra fat around their buttocks, legs, or abdomen.

Depending on your age and the type of lipodystrophy syndrome you have, you might not notice any health issues for years. Regular blood tests, such as a lipid panel and a basic metabolic panel, may reveal elevated levels of cholesterol, triglycerides, and blood sugar (glucose) caused by various forms of lipodystrophy.

It might be challenging to identify certain forms of lipodystrophy, particularly partial lipodystrophies. Because of this, regardless of the reason, it’s critical to consult your healthcare professional if you or your kid are having new or worsening symptoms at any time.

Causes genetic forms of lipodystrophy

Congenital generalized lipodystrophy and familial partial lipodystrophy are two hereditary types of lipodystrophy that are caused by certain genetic abnormalities.

A genetic mutation is an alteration in your DNA’s sequence. Your cells get the information they require to carry out their tasks from your DNA sequence. You may have signs of a genetic disorder if a portion of your DNA sequence is incomplete or damaged.

cause of congenital generalized lipodystrophy (CGL):

Congenital generalized lipodystrophy types 1 through 4 are caused by mutations in the AGPAT2, BSCL2, CAV1, and CAVIN1 genes, respectively. These genes are crucial for the growth and functions of adipocytes, the cells in your adipose tissue that store fat. Adipocyte structure and function are impacted by mutations in these genes.

The gene mutations that cause CGL are inherited by a child from their biological parents. Although each parent carries one copy of the defective gene, they usually do not exhibit symptoms.

cause of familial partial lipodystrophy (FPLD):

Mutations in the LMNA gene are the most prevalent cause of familial partial lipodystrophy.

Instructions for producing proteins with a range of uses, including crucial roles in adipocytes and fat storage, are provided by LMNA and the other genes linked to FPLD. Adipocyte formation, structure, or function is all adversely affected by mutations in any of these genes.

One copy of the mutant gene in each cell is sufficient to induce FPLD, as the majority of cases are inherited in an autosomal dominant manner. A person with FPLD may occasionally inherit the mutation from one of their biological parents. Other occurrences occur in persons who have no family history of the disorder and are caused by novel, random mutations in the gene.

Causes of acquired forms of lipodystrophy:

Medications, autoimmune responses, or an unidentified cause (idiopathic) can all result in acquired lipodystrophies. Although there is no obvious genetic foundation for acquired lipodystrophies, some researchers believe that some individuals may be genetically predisposed to acquiring specific types of acquired lipodystrophy.

Causes of acquired generalized lipodystrophy (AGL):

AGL may develop after an autoimmune condition or infection. The following infections have been linked to the development of AGL:

• Varicella, or chickenpox.
• measles.
• whooping cough (pertussis).
• diphtheria.
• pneumonia.
• osteomyelitis.
• Mononucleosis (mono).
• It’s not a guarantee that you’ll get AGL if you’ve had any of these diseases.

Among the autoimmune diseases associated with AGL are:

• autoimmune thyroid disease.
• Autoimmune Hepatitis.
• Childhood dermatomyositis.
• Rheumatoid arthritis.
• Sjogren’s syndrome.
• hemolytic anemia caused by autoimmune disease.
• AGL does not always follow from having any of these autoimmune diseases.

AGL is frequently idiopathic, meaning its cause is unknown.

Causes of acquired partial lipodystrophy (APL):

According to scientists, APL is caused by your immune system unintentionally eliminating fat cells. Over 80% of individuals with APL have reduced blood levels of complement 3, a protein factor that typically contributes to the body’s immunological response.

Additionally, individuals with APL frequently contain complement 3-nephritic factor, an autoantibody, in their blood. An immune system protein known as an autoantibody unintentionally attacks and harms healthy tissue.

Cause of high active antiretroviral therapy (HAART) induced lipodystrophy (LD-HIV):

The precise cause of lipodystrophy caused by HIV-1 protease inhibitor-containing HAART, an antiretroviral therapy, remains unknown.

The good news is that because newer HIV drugs are less likely to produce lipodystrophy, most persons starting HIV therapy today don’t have to worry about it.

Lipodystrophy Diagnosis

To confirm a diagnosis or rule out other potential causes of your symptoms, your healthcare provider will do a physical examination, ask thorough questions about your medical and family history, and request specific tests if you show symptoms of lipodystrophy.

What diagnostic procedures will be used to identify lipodystrophy?

To help diagnose lipodystrophy and/or rule out other illnesses that might be causing your symptoms, your doctor might prescribe several tests. Among these exams could be:

• MRI (magnetic resonance imaging) scan of the entire body: An MRI creates comprehensive pictures of your body’s organs and other structures using radio waves, a big magnet, and a computer. This imaging test may be ordered by your doctor to determine the distribution and composition of fat in your body.
• Comprehensive metabolic panel: A blood sample test called a complete metabolic panel evaluates 14 distinct chemicals in your blood. In particular, your doctor will be examining your liver enzyme and blood sugar (glucose) readings.
• Lipid panel: A lipid panel is a blood test that quantifies your blood’s concentration of certain fat molecules known as lipids. The panel typically includes a triglyceride test in addition to four distinct cholesterol readings. Abnormal cholesterol levels are frequently the result of lipodystrophy.
• Leptin test: This blood test determines your blood’s leptin level. Your body’s adipose tissue, or body fat, releases the hormone leptin, which aids in long-term weight maintenance. Lower-than-normal leptin levels may indicate how your body reacts to leptin replacement therapy if you have lipodystrophy.
• Genetic examination: Your doctor can suggest genetic testing to confirm the diagnosis if they think you have an inherited (genetic) type of lipodystrophy.
• Renal biopsy: In this procedure, a sample of kidney tissue is surgically removed and examined under a microscope. This test may be ordered by your doctor to determine whether lipodystrophy affects your kidneys.

lipodystrophy treatment

The type of lipodystrophy you have and if you have any concomitant diseases, including diabetes or high cholesterol levels, will determine how you are treated and managed.

The following are typical lipodystrophy management therapies:

• Leptin replacement drug: A synthetic form of the fat hormone leptin, metreleptin, may be prescribed by your doctor. Leptin deficiency is common in people with lipodystrophy. This hormone can assist in lowering elevated triglyceride and cholesterol levels as well as regulate your body’s metabolic processes.
• Treatment for diabetes and insulin resistance: Your doctor may recommend oral medications such as pioglitazone, metformin, sulfonylureas, or thiazolidinediones if you have diabetes and/or insulin resistance as a result of lipodystrophy. To manage diabetes, certain lipodystrophy patients may need to take synthetic insulin. You’ll probably also need to use an at-home glucometer to periodically monitor your blood sugar levels.
• Controlling triglyceride and cholesterol levels: In addition to treating diabetes, the oral drugs listed above frequently aid in controlling cholesterol. Statins like rosuvastatin and pravastatin may also be prescribed by your physician. Fibric acid derivatives or n-3 polyunsaturated fatty acid supplements derived from fish oils may be necessary for those with severe hypertriglyceridemia.
• Cosmetic surgery and procedures: To improve their appearance and self-confidence, people with lipodystrophy in aesthetically sensitive places like their face, chest, or pubic region may undergo cosmetic surgery. Autologous adipose tissue transplantation, free flap face restoration, and silicone or other implants in areas lacking fat tissue are all options available to plastic surgeons. They can remove undesired excess fat from body regions like your chin or the back of your neck (commonly referred to as your “buffalo hump”) by liposuction or surgical excision.
• Researchers still need to understand more about managing and treating lipodystrophy. There will probably be additional therapy choices available as they learn more about the intricacies of metabolic processes.

Prevention

For the most part, lipodystrophy cannot be prevented.

Since genetic forms of lipodystrophy are caused by inherited genetic mutations, they cannot be prevented. If you intend to become pregnant, discuss genetic testing with your healthcare provider to determine your risk of having a child with a genetic problem.

Infections and autoimmune diseases are common causes of acquired forms of lipodystrophy. Vaccinations help prevent some infections, such as whooping cough (pertussis) and chickenpox, but they cannot prevent conditions linked to autoimmune diseases and acquired lipodystrophy.

FAQs

References:

• Lipodystrophy. (2025b, October 20). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/23441-lipodystrophy
• Wikipedia contributors. (2025e, December 21). Lipodystrophy. Wikipedia. https://en.wikipedia.org/wiki/Lipodystrophy