Lipodystrophy: Types, Causes, Symptoms & Treatment

Location is everything. As we learn more all the time, disorders of weight and metabolism are about more than the amount of fat on a body—it’s also the location of fat that matters. And, just as too much fat can pose health issues, so can too little. Lipodystrophy syndromes—which we’ll refer to collectively as lipodystrophy—deal with a loss of or abnormal distribution of adipose tissue.

Lipodystrophy is linked with metabolic diseases such as diabetes and fatty liver disease and can lead to life-threatening complications. It can also cause visible fat deposits just beneath the skin on the neck, face, legs, and elsewhere, which can cause self-consciousness.

*** Prevalence of Lipodystrophies are challenging to calculate due to multiple reasons: underdiagnosis due to overlapping symptoms with other conditions, decreased awareness and understanding of the disease**

Estimates vary widely on the number of people in the U.S. affected, ranging from one to five million. To best support patients, it is helpful to know what lipodystrophy is, what causes it, how to diagnose it, and how to treat or manage it. In addition, these diseases add to our understanding of adipose tissue and adipokines, potentially enhancing our ability to treat obesity, diabetes, and other metabolic conditions.

What is Lipodystrophy?

Per Yale Medicine, “Lipodystrophy is a group of rare syndromes that cause a person to lose fat from some parts of the body, while gaining it in others, including on organs like the liver.” As we know, adipose tissue plays an important role in maintaining healthy blood sugar levels and energy homeostasis.

The hormone leptin, an adipokine, helps the body process glucose and lipids. Without enough leptin, these substances build up in the blood and disrupt metabolic processes. In some cases, the body stores excess fat in the liver, pancreas, and/or skeletal muscle, where it causes problems including inflammation. For example, inflammation in perimuscular fat is associated with insulin resistance. Adipokines also play a role in blood pressure regulation and cardiovascular homeostasis.

The loss of fat alone is called lipoatrophy, and it may or may not be a part of lipodystrophy. Either may be associated with sarcopenia, which is a loss of muscle mass. Lipodystrophy can be congenital or acquired and each type can be generalized or partial.

Types and Causes of Lipodystrophy

The cause of lipodystrophy depends on the type. There are multiple types of both congenital (hereditary) and acquired lipodystrophy.

Congenital types of lipodystrophy

These forms of lipodystrophy typically present symptoms soon after birth.

• Congenital generalized lipodystrophy (CGL) is a rare disorder in which the body does not make adipose tissue. It also goes by the name Berardinelli-Seip syndrome (BSCL). Mutations in the leptin gene cause a leptin deficiency resulting in a near-total lack of body fat from birth. It has four subtypes, each associated with a particular gene. In early 2025, the California Institute for Regenerative Medicine (CIRM) awarded Entos Pharmaceuticals a $4 million grant to support their development of a treatment for CGL.

• Familial partial lipodystrophy (FPLD) is another rare genetic condition. Instead of an absence of fat, a child may exhibit excess fat deposits on the face or neck. The signs tend to become more visible as a child ages and sometimes abnormal fat distribution does not begin until adulthood. The syndrome has various subtypes.

Acquired types of lipodystrophy

Acquired lipodystrophy syndromes are often triggered by an infection or autoimmune condition, but even these may have a genetic component.

• Acquired generalized lipodystrophy (AGL) is also known as Lawrence-Seip syndrome or simply Lawrence Syndrome. It can occur at any age but is extremely rare. Like CGL, it is marked by a near-total absence of adipose tissue.

• Barraquer-Simons syndrome (BSS) is acquired but partial. Also very rare, it is characterized by gradual subcutaneous fat loss. Fat loss occurs symmetrically from the head down the trunk.

• Other lipodystrophy syndromes may be related to the injection of drugs, antiretroviral therapy for HIV, or autoimmune disorders, or they may be idiopathic. Since the causes vary, these can develop at any age.

Symptoms and Diagnosis

Lipodystrophy often co-occurs with other conditions, so separating it can be a challenge. However, some symptoms are striking, particularly in the general types.

Recognizing Symptoms of Lipodystrophy

In congenital forms like CGL, lipodystrophy may be visible through simple visual observation within the first year of life. Babies born with CGL tend to display:

• A muscular appearance with slightly enlarged jaw, feet, and hands

• A strong appetite

• Rapid growth

• Dark, velvety skin in the armpits, neck, and groin

• An enlarged belly button or bulging around the belly button

With partial forms, the signs may not be visible as early, depending on the parts of the body affected.

In adolescents or adults, the first signs may be high levels of cholesterol, triglycerides, and/or glucose. In seeking underlying causes of these issues, lipodystrophy may come to light, sometimes through a process of ruling out other causes.

Acquired types of lipodystrophy may follow:

• An infection such as measles, pneumonia, chicken pox, or whooping cough

• An autoimmune disease such as rheumatoid arthritis or autoimmune hepatitis

• The use of injectable drugs

• Treatment for HIV with antiretroviral drugs

Diagnostic Procedures of Lipodystrophy

The conversation may begin when normal treatment for hyperglycemia or hypertriglycemia is ineffective. The person may also struggle with high cholesterol or may report a disordered appetite. Fat deposits may be visible on the face, neck, or other unusual areas. Family history may reveal clues to congenital forms, especially FPLD, which only requires one copy of a mutated gene, while CGL requires two (i.e., both parents).

It makes sense to start with a full metabolic panel and lipid panel. A whole-body MRI can provide more insight into fat distribution. Occasionally, a biopsy of an affected organ may be informative.

Genetic testing

With advances in genetic testing, we can learn more about a person’s underlying health than ever before. There are 12 genes known to be associated with congenital lipodystrophy:

• AGPAT2

• BSCL2

• CAV1

• CAVIN1

• FBN1

• KCNJ6

• LIPE

• LMNA

• PIK3R1

• PLIN1

• PPARG

• ZMPSTE24

Mutations on these can aid in a diagnosis. However, the possibility exists that other not-yet-identified genes may play a role, so some thought leaders suggest taking a wider view.

A 2024 publication suggests:

“When commercial panels are not positive, an attempt for whole exome or even whole genome testing with mitochondrial gene evaluation has evolved as viable and increasingly more available strategies. If these latter tests cannot be undertaken commercially, ongoing research in specialty centers can be considered where pipelines to analyze VUS (variant of uncertain significance) and evaluate transcriptomic profiles from PBMCs or tissues may be considered.”

Treatment and Management Strategies

There is no cure for lipodystrophy, so treatment usually focuses on comorbidities. Medications and lifestyle modifications each play a role.

Lifestyle and Dietary Modifications

A person with lipodystrophy should follow a diet low in processed foods, fats, and sugars, and high in fiber, fresh fruits and vegetables. The Mediterranean diet or similar program fits the bill. They should also engage in regular cardiovascular exercise to boost cardiovascular and metabolic health.

Some patients choose cosmetic surgery to address the appearance of fat deposits.

Medications

One medical approach is leptin replacement therapy. Metreleptin, a synthetic version of leptin, can be prescribed to help stabilize metabolic processes. It may reduce high cholesterol and triglyceride levels.

Physicians treating obesity may be interested to note that leptin-targeted therapies are being investigated for their potential to treat obesity and other metabolic diseases. (Meanwhile, over-the-counter supplements marketed as “leptin supplements” are typically a mixture of herbs and caffeine with little to no evidence of effectiveness.)

Medications also address comorbidities, including insulin resistance, type 2 diabetes, and hypercholesterolemia. People with diabetes and lipodystrophy may be treated with oral medications like pioglitazone metformin, sulfonylureas, or thiazolidinediones, or with synthetic insulin. They should be taught how to monitor their blood sugar levels at home.

Statins, such as rosuvastatin and pravastatin, can be used to treat hypercholesterolemia. Extreme hypertriglyceridemia may call for fibric acid derivatives or n-3 polyunsaturated fatty acids supplementation from fish oils.

Psychological and Social Considerations

Research into quality of life with lipodystrophy is limited. Because it often causes changes to a person’s appearance, lipodystrophy can cause self-consciousness, potentially leading to mental health challenges. A study published in 2024 in Orphanet Journal of Rare Diseases attempted to quantify some of the impacts, albeit from a small sample.

Researchers assessed a group 67 adults and eight children living with lipodystrophy over the course of two years. Among 65 adults who agreed to a psychiatric assessment, 18 were diagnosed with a psychiatric disorder. More than a third of the participants reported depression symptoms on the Beck Depression Inventory. Appetite problems, ADHD, and self-consciousness about physical appearance were other common concerns.

Prognosis and Long-term Management

What is the Prognosis for Lipodystrophy?

While there is no cure for lipodystrophy, leptin replacement therapy can help manage it. Comorbidities, from diabetes to depression, must be addressed independently. Cosmetic surgery can help with appearance.

A person living with lipodystrophy may face a wide range of complications:

• Insulin resistance and diabetes

• Dyslipidemia and pancreatitis

• Liver complications

• Kidney complications

• Cardiac complications

• Neuromusculoskeletal complications

• Polycystic ovary syndrome

• Fertility issues

** A review published in journal of clinical concluded that the adipose tissue impairment associated with lipodystrophy presents with the same conditions as the metabolic syndrome. Although , management will be similar, differentiation between conditions will be necessary to ensure a complete treatment plan.**

They will need careful monitoring of their condition or conditions throughout their lives and have a low life expectancy. One study found that lipodystrophy decreased the average life span by 36 years. Other sources put life expectancy at no more than 50 years.

Monitoring and Follow-up

Early diagnosis can give the best chance of recognizing and treating comorbidities. It’s highly important for a person with lipodystrophy to have regular monitoring of their primary condition and any others that arise alongside it.

Final Thoughts

Although rare, lipodystrophy syndromes present a great challenge to those who live with them and their medical teams. Greater understanding of these conditions can allow for better care and support of those who have them. In addition, studying conditions related to adipose tissue, leptin, and other interconnected processes can shed light on the much more common diseases of obesity and diabetes.

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Other FAQs

What is the Difference Between Generalized and Partial Lipodystrophy?

Generalized lipodystrophy means the absence of fat tissue, while partial lipodystrophy can mean that fat tissue is lost in some parts of the body and/or is translocated to other parts. Either type may be genetic or acquired.

Can Lipodystrophy Be Prevented?

Lipodystrophy cannot be prevented. Some infections that lead to acquired forms, like chicken pox and whooping cough, can be prevented with vaccinations.

How Does Lipodystrophy Affect Metabolic Health?

Lipodystrophy affects the body’s ability to process sugars and cholesterol, leading to appetite dysfunction, insulin resistance, and other metabolic concerns. These effects are largely due to the absence of leptin and to the body’s tendency to store fat around organs such as the liver.

How Can I Connect With Others Who Have Lipodystrophy?

The National Organization for Rare Disorders (NORD) offers resources to those with acquired and congenital types of lipodystrophy.

Can You Live a Long Life With Lipodystrophy?

Estimates vary, but it is largely accepted that the disease and its complications can significantly shorten life expectancy.

Are There Any New Treatments on The Horizon for Lipodystrophy?

Genetic medicine is still in its infancy and may provide greater insight, including the potential to develop treatments for genetic forms of lipodystrophy. Furthermore, the understanding of leptin is still developing and could potentially lead to new breakthroughs.