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Lipodystrophy

  • A group of rare diseases that cause abnormal distribution of fat throughout a person's body
  • Most common symptom is noticeable and consistently decreasing fat in some regions on the body
  • Treatment includes dietary changes to help manage symptoms
  • Involves digestive diseases

Overview

Body fat plays a vital role in human health. The fat, or adipose, tissue just underneath our skin keeps us warm and provides protective cushioning. It also helps maintain healthy sugar levels in the blood, a complex metabolic process.  

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. A person can be born with lipodystrophy or develop it later in life. In either case, the resulting inability to maintain fat tissue beneath the skin can have severe, life-threatening consequences over time.

Health complications usually begin early in the disease process, because with little fat—and therefore low levels of its accompanying hormone, leptin—the body has a difficult time properly processing sugar (glucose) and fats (lipids). As a result, these substances build up in the bloodstream, which usually leads to the development of diabetes (due to consistently high sugar levels) and a higher risk of cardiovascular disease (due to cholesterol build-up in the arteries).

Yale Medicine’s physicians, who have expertise in rarely seen disorders, work to ensure that lipodystrophy is detected as early as possible.  

What is lipodystrophy?

Lipodystrophy syndromes are rare disorders marked by a lack of body fat just beneath the skin’s surface. Which type a person has is determined by the patterns of fat loss on the body and whether the disease is acquired or genetic. Due to the body’s inability to process fat, lipodystrophy leads to severe metabolic, hormonal, cardiovascular and fat storage disorders. Because the disease affects an individual’s outward appearance, it can also have deep psychological effects that may need to be addressed by a mental health care professional.

People who have lipodystrophy can end up with extra fat deposits in their legs, on the face, the back of the neck, or abdomen, and within the liver (called non-alcoholic fatty liver disease). This happens because the body is unable to maintain a layer of fat beneath the skin’s surface, so the fat he or she consumes concentrates elsewhere in the body.  

What types of lipodystrophy exist?

The first type of lipodystrophies includes those that are present at birth: 

  • Congenital generalized lipodystrophy (CGL) is caused by a genetic mutation and can often be detected within the first year of a child’s birth. This is because the body’s inability to form fat tissue may make a child’s muscles and veins more visible. A person with CGL may develop hyperphagia—a term to describe excessive hunger (and overeating)—possibly due to low levels of the fat hormone called leptin. People with this subtype are likely to develop diabetes due to an early struggle with high sugar (glucose) levels in the blood. 
  • Familial partial lipodystrophy (FPLD) is also a genetic condition but can be more difficult to diagnose due to a child’s normal-seeming appearance at birth and during early childhood. However, as the child ages, the fat loss becomes noticeable, and excess fat deposits may show up in other areas of the body, such as the face, neck, or, less noticeably, visceral fat in the abdomen, which is hidden beneath the abdominal muscles. Women with FPLD may experience menstrual irregularity, but not infertility.

The second type of this disease includes patients who acquire it during their lifetime: 

  • Acquired generalized lipodystrophy (AGL) can be especially difficult to detect given its progression of fat tissue loss, typically starting in teenage years. (In rare cases, patients have developed the condition after age 30). AGL affects about three times as many women as men. While sources of the disorder vary, some potential reasons it might develop include panniculitis (a rare skin disorder that affects the layer of fat beneath the skin) and autoimmune diseases like juvenile dermatomyositis (an inflammatory disease that affects the skin, muscles, and blood vessels). Those with this subtype of the disease suffer from high triglyceride (a type of fat) levels and type 2 diabetes. 
  • Acquired partial lipodystrophy (APL) typically affects only the upper body, including the face and neck. The subtype of this disease is four times more common in women and patients tend to begin losing fat in childhood or teenage years. Some individuals may carry excess fat around their abdomen, legs or the buttocks. Unlike other subtypes, APL is less often linked to metabolic complications, but it can severely damage the kidneys due to fat accumulation (and resulting inflammation) on the organ. APL has also been associated with autoimmune diseases like dermatomyositis, lupus and proteinuria (which is defined as detectable protein in the urine). 

What are the symptoms of lipodystrophy?

The most common symptom is a noticeable and consistently decreasing amount of fat in some regions on the body. Depending on the type of lipodystrophy syndrome and a person’s age, he or she may not experience health problems for years. Those who have a subtle subtype of the syndrome may show unusually and inexplicably high levels of cholesterol, triglycerides, and glucose from routine blood tests. The symptoms also range in severity, from an insatiable appetite on one end, to excruciating pain due to pancreatitis (inflammation of the pancreas) on the other.   

How is it diagnosed?

A physician will diagnose the disease based on a number of factors, including a physical exam, a family history of medical conditions, body fat composition gathered from a whole-body MRI, and the presence of any metabolic disorders, like diabetes. Another sign may be if a patient suffers from hyperglycemia (too much sugar in the blood) or hypertriglyceridemia (too many triglycerides in the blood) that is resistant to normal treatment. A physician may suggest genetic testing or whole-exome sequencing if he or she suspects you have a genetic form of lipodystrophy. 

What treatment options are available for lipodystrophy?

A strict, low-fat diet and exercise program is recommended as a starting point to manage the condition. While recommendations vary, patients are urged to follow a Mediterranean-style diet that is low in processed foods, fats and sugars, and high in fiber, fresh fruits and vegetables. The primary drug used to manage lipodystrophy is called metreleptin, a synthetic version of the fat hormone, leptin (which is usually made and stored in adipose tissue). This hormone helps orchestrate the metabolic processes of the body and can help reduce high cholesterol and triglyceride levels. 

While there is no cure for lipodystrophy, the conditions that frequently accompany it, like diabetes, can be managed. Patients may also explore cosmetic surgery to address the uneven distribution of fat throughout their body. 

What makes Yale Medicine unique in treating this disease?

Yale Medicine brings together multi-disciplinary expertise for management of lipodystrophy syndromes. Our physicians have a long track record of research on the mechanisms underlying lipodystrophy and management of its complications, including diabetes, elevated blood lipid levels and fat accumulation in the liver. “Our work aims to increase awareness of lipodystrophic syndromes within the large landscape of fatty liver disease, otherwise known as non-alcoholic fatty liver disease (NAFLD),” says Silvia Vilarinho, MD, PhD, a physician-scientist in the digestive diseases department.