Lipodystrophy

Lipodystrophy

Overview

Lipodystrophy is a general term for a group of conditions that are characterized by a complete (generalized) or partial loss of fat tissue (adipose tissue) in certain areas of your body and/or abnormal distribution of fat tissue.

There are multiple types of lipodystrophy, which may be either genetic (caused by a genetic mutation) or acquired (caused by another condition).

The types of lipodystrophy affect people differently and have several different symptoms.

What is the function of adipose tissue?

You have adipose tissue (fat tissue) throughout your body, including beneath your skin and around your internal organs. Adipose tissue serves many important functions, including:

Storing calories for energy.

Providing cushioning for various parts of your body.

Providing insulation (keeping your body warm).

Releasing certain hormones, such as leptin.

Moderating inflammation.

A loss and/or redistribution of body fat due to lipodystrophy can cause significant changes in your appearance, but it also affects certain important metabolic functions in your body. Many people with lipodystrophy develop diabetes and have irregular cholesterol levels.

What are the types of lipodystrophy?

There are several different types of lipodystrophy, which can be organized into two main categories: genetic and acquired.

Genetic forms of lipodystrophy

The genetic forms of lipodystrophy include:

Congenital generalized lipodystrophy (CGL): Congenital generalized lipodystrophy (also called Berardinelli-Seip syndrome) is a rare type of lipodystrophy with significant and sometimes near-total fat loss. This condition is caused by a genetic mutation (change) that you’re born with. It’s often diagnosed within the first year of life.

Familial partial lipodystrophy (FPLD): Familial partial lipodystrophy is also genetic (inherited). It’s often diagnosed later in a child’s life. Fat loss mainly affects a child’s legs and arms with excess fat in their face and neck.

Acquired forms of lipodystrophy

The acquired forms of lipodystrophy include:

Acquired generalized lipodystrophy (AGL): Acquired generalized lipodystrophy (also called Lawrence syndrome) usually results in fat loss in your face, neck, arms and legs. Fat loss associated with AGL may occur rapidly over a few weeks or slowly over several months or even years. It usually develops during childhood or adolescence but can occur at any age. AGL has multiple possible causes.

Acquired partial lipodystrophy (APL): Acquired partial lipodystrophy (also called Barraquer-Simons syndrome), is characterized by gradual loss of fat from your face, neck, arms and chest during childhood. Some people with APL may carry excess fat around their abdomen (belly), legs or buttocks. APL is often associated with autoimmune conditions.

High active antiretroviral therapy (HAART) induced lipodystrophy (LD-HIV): This form of lipodystrophy occurs in people with human immunodeficiency virus (HIV) after receiving antiretroviral therapy known as HIV-1 protease inhibitor-containing HAART. The development of lipodystrophy is related to the intensity and length of treatment. In most cases, people with LD-HIV gradually lose fat from their arms, legs and face. Some people may develop excess fat in their face, neck, upper back and waist.

Localized lipodystrophy: This form of lipodystrophy results in fat loss in a small area of your body only. It may result at a common site for medication injection (such as insulin injections). Localized lipodystrophy looks like a dimple or crater with the overlying skin usually unaffected.

How does lipodystrophy affect my body?

Each type of lipodystrophy affects your body differently. The two main aspects of lipodystrophy that typically affect anyone with the condition include the loss of adipose tissue and a lack of the hormone leptin.

The effects of adipose tissue loss on your body

Adipose tissue (body fat) is made up of cells called adipocytes. Each adipocyte has a lipid droplet that accounts for approximately 90% of its cell volume. An adipocyte stores fats (triglycerides) within its lipid droplet. Lipodystrophy causes damage to adipose tissue, which prevents proper fat storage.

In some cases of lipodystrophy, your body improperly stores the fat lost from your adipose tissue in other tissue of your body, such as your liver, pancreas and/or skeletal muscle. This can lead to certain health conditions, including:

Fatty liver disease (hepatic steatosis).

Insulin resistance and hyperinsulinemia (higher-than-normal insulin levels).

Diabetes.

Hypertriglyceridemia (elevated triglyceride levels).

Pancreatitis.

Metabolic syndrome.

Coronary artery disease.

Not everyone with lipodystrophy will develop these conditions, and some people may have more mild or severe cases of them.

The effects of leptin deficiency on your body

In people with lipodystrophy, a loss of adipose tissue (body fat) leads to a lack of certain hormones — in particular, leptin.

Leptin is a hormone your adipose tissue releases that helps your body maintain your normal weight on a long-term basis. It does this by regulating hunger by providing the sensation of satiety (feeling full). Scientists are still studying leptin, and they believe it also affects your metabolism, endocrine system regulation and immune system function.

People with lipodystrophy often have a decrease in leptin levels, which can cause extreme hunger, insulin resistance and other health conditions.

Symptoms

As there are so many types of lipodystrophy, its symptoms vary widely.

The most common symptom of lipodystrophy is a noticeable and consistently decreasing amount of fat in some regions of your body with normal or comparatively excess amounts of fat in other regions of your body.

For example, people with acquired partial lipodystrophy (APL) typically have a gradual loss of fat from their face, neck, arms and chest during childhood. Some people with APL may have excess fat around their belly, legs or buttocks.

Depending on the type of lipodystrophy syndrome you have and your age, you may not experience noticeable health problems for years. Multiple types of lipodystrophy cause high levels of cholesterol, triglycerides and blood sugar (glucose), which your healthcare provider may discover from routine blood tests, such as a lipid panel and a basic metabolic panel.

Some types of lipodystrophy, especially partial lipodystrophies, can be difficult to detect. Because of this, it’s important to see your provider if you or your child are experiencing new or worsening symptoms at any time — no matter what the cause may be.

Causes

The genetic forms of lipodystrophy — congenital generalized lipodystrophy and familial partial lipodystrophy — are caused by certain genetic mutations (changes).

A genetic mutation is a change in a sequence of your DNA. Your DNA sequence gives your cells the information they need to perform their functions. If part of your DNA sequence isn’t complete or is damaged, you might experience symptoms of a genetic condition.

The cause of congenital generalized lipodystrophy (CGL)

Mutations in the AGPAT2, BSCL2, CAV1 and CAVIN1 genes cause congenital generalized lipodystrophy types 1 through 4, respectively. These genes play important roles in the development and function of adipocytes, the fat-storing cells in your adipose tissue. Mutations of these genes affect the structure and function of adipocytes.

A child with CGL inherits the gene mutations from their biological parents. The parents each have each carry one copy of the mutated gene, but they typically don’t show signs and symptoms of the condition.

The cause of familial partial lipodystrophy (FPLD)

Familial partial lipodystrophy can be caused by mutations in several genes — most commonly, mutations in the LMNA gene.

LMNA and the other genes associated with FPLD provide instructions for making proteins with a variety of functions, including important roles in fat storage and adipocytes. Mutations in any of these genes negatively affect the development, structure or function of adipocytes.

Most cases of FPLD are inherited in an autosomal dominant pattern, which means one copy of the mutated gene in each cell is enough to cause the condition. In some cases, a person with FPLD inherits the mutation from one affected biological parent. Other cases result from new, random mutations in the gene and occur in people with no history of the condition in their family.

What are the causes of acquired forms of lipodystrophy?

Acquired lipodystrophies can be caused by medications, autoimmune reactions or have an unknown cause (idiopathic). While acquired lipodystrophies don’t have a direct genetic basis, some researchers think that some people may have a genetic predisposition for developing certain forms of acquired lipodystrophy.

Causes of acquired generalized lipodystrophy (AGL)

AGL may occur following an infection or autoimmune disease. Infections that have been associated with the development of AGL include:

Chickenpox (varicella).

Measles.

Whooping cough (pertussis).

Diphtheria.

Pneumonia.

Osteomyelitis.

Mononucleosis (mono).

If you’ve had any of these infections, it doesn’t necessarily mean that you’ll develop AGL.

Autoimmune conditions that have been linked to AGL include:

Autoimmune thyroiditis.

Autoimmune hepatitis.

Juvenile dermatomyositis.

Rheumatoid arthritis.

Sjogren’s syndrome.

Autoimmune hemolytic anemia.

If you have any of these autoimmune conditions, it doesn’t necessarily mean that you’ll develop AGL.

In many cases, the cause of AGL is unknown (idiopathic).

Causes of acquired partial lipodystrophy (APL)

Scientists believe APL is caused by your immune system mistakenly destroying fat cells. More than 80% of people with APL have low levels of complement 3, a protein factor that normally plays a role in your body’s immune system response, in their blood.

People with APL also often have an autoantibody in their blood called complement 3-nephritic factor. An autoantibody is an immune system protein that mistakenly targets and damages healthy tissue.

The cause of high active antiretroviral therapy (HAART) induced lipodystrophy (LD-HIV)

Scientists aren’t sure of the exact reason why antiretroviral therapy known as HIV-1 protease inhibitor-containing HAART causes lipodystrophy.

The good news is that lipodystrophy isn’t a concern for most people who start HIV treatment now because newer HIV medications are less likely to cause the condition.

Diagnosis

If you have symptoms of lipodystrophy, your healthcare provider will perform a physical exam, ask detailed questions about your medical and family history, and order certain tests to confirm a diagnosis or rule out other possible causes of your symptoms.

What tests will be done to diagnose lipodystrophy?

Your provider may order several tests to help diagnose lipodystrophy and/or rule out other conditions that could be causing your symptoms. These tests could include:

Whole-body MRI (magnetic resonance imaging) scan: MRI uses a large magnet, radio waves and a computer to produce detailed images of organs and other structures inside of your body. Your provider may order this imaging test to assess your body’s fat composition and distribution.

Comprehensive metabolic panel: A comprehensive metabolic panel is a blood sample test that measures 14 different substances in your blood. It provides important information about your body’s chemical balance and metabolism. Your provider will be specifically looking at the measurements for your blood sugar (glucose) and liver enzymes.

Lipid panel: A lipid panel is a blood test that measures the amount of certain fat molecules called lipids in your blood. In most cases, the panel includes four different cholesterol measurements and a measurement of your triglycerides. Lipodystrophy often causes abnormal cholesterol levels.

Leptin test: This is a blood test that measures the level of leptin in your blood. Leptin is a hormone your adipose tissue (body fat) releases that helps your body maintain your normal weight on a long-term basis. If you have lipodystrophy and have lower-than-normal leptin levels, it may predict how your body responds to leptin replacement treatment.

Genetic testing: If your provider suspects you have an inherited (genetic) form of lipodystrophy, they may recommend genetic testing to confirm the diagnosis.

Kidney (renal) biopsy: This test involves the surgical removal and microscopic examination of a sample of kidney tissue. Your provider may order this test to assess if your kidneys are affected by lipodystrophy.

Treatment

The treatment and management of lipodystrophy depend on which specific type you have and if you have any associated conditions, such as diabetes or abnormal cholesterol levels.

Common management therapies for lipodystrophy include:

Leptin replacement medication: Your provider may prescribe metreleptin, a synthetic version of the fat hormone, leptin. People with lipodystrophy often have a lack of leptin. This hormone helps control your body’s metabolic processes and can help reduce high cholesterol and triglyceride levels.

Diabetes and insulin resistance treatment: If you have insulin resistance and/or diabetes due to lipodystrophy, your provider may prescribe oral medication to help treat it, such as pioglitazone metformin, sulfonylureas or thiazolidinediones. Some people with lipodystrophy may need to take synthetic insulin to treat diabetes. You’ll likely need to check your blood sugar levels regularly with an at-home glucometer as well.

Regulating triglyceride and cholesterol levels: The oral medications mentioned above that can help treat diabetes can often also help regulate cholesterol levels. Your provider may also prescribe statins, such as rosuvastatin and pravastatin. People with extreme hypertriglyceridemia may need to take fibric acid derivatives or n-3 polyunsaturated fatty acids supplementation from fish oils.

Cosmetic surgery and procedures: People with lipodystrophy in cosmetically sensitive areas, such as their face, chest or pubic region, may get cosmetic surgery to help with their appearance and self-confidence. Plastic surgeons can use autologous adipose tissue transplantation, facial reconstruction with free flaps and silicone or other implants in areas where fat tissue is missing. They can use liposuction or surgical excision for removing unwanted excess fat from body parts such as your chin or the back of your neck (often called “buffalo hump”).

Scientists still have more to learn about how to treat and manage lipodystrophy. As they discover more about the complexities of metabolic processes, more treatment options will likely become available.

Type of Doctor Department : General Physician or Pediatrician ,an Endocrinologist (hormones/metabolism), a Lipidologist (fat/triglycerides), or Dermatologist