Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the body's

adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

. A more specific term, '' lipoatrophy ("lipo" is

Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...

for "fat", and "dystrophy" is Greek for "abnormal or degenerative condition")'', is used when describing the loss of fat from one area (usually the face). This condition is also characterized by a lack of circulating leptin which may lead to osteosclerosis. The absence of fat tissue is associated with

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood suga ...

, hypertriglyceridemia, non-alcoholic fatty liver disease (NAFLD) and

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrom ...

Types

Lipodystrophy can be divided into the following types: *Congenital lipodystrophy syndromes ** Congenital generalized lipodystrophy (Berardinelli-Seip syndrome) **

Familial partial lipodystrophy Familial partial lipodystrophy, also known as Köbberling–Dunnigan syndrome, is a rare genetic metabolic condition characterized by the loss of subcutaneous fat. FPL also refers to a rare metabolic condition in which there is a loss of subcutane ...

** Marfanoid–progeroid–lipodystrophy syndrome ** Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome *Acquired lipodystrophy syndromes ** Acquired partial lipodystrophy (Barraquer-Simons syndrome) ** Acquired generalized lipodystrophy ** Centrifugal abdominal lipodystrophy (Lipodystrophia centrifugalis abdominalis infantilis) ** Lipoatrophia annularis (Ferreira-Marques lipoatrophia) ** Localized lipodystrophy ** HIV-associated lipodystrophy

Epidemiology

Congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities c ...

lipodystrophy (due to inherited genetic defect) is estimated to be extremely rare, possibly affecting only one per million persons. Acquired lipodystrophy is much more common, especially affecting persons with

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...

infection.

Pathogenesis

Due to an insufficient capacity of subcutaneous

to store fat, fat is deposited in non-adipose tissue ( lipotoxicity), leading to

. Patients display hypertriglyceridemia, severe fatty liver disease and little or no adipose tissue. Average patient lifespan is approximately 30 years before death, with liver failure being the usual cause of death. In contrast to the high levels seen in non-alcoholic fatty liver disease associated with obesity, leptin levels are very low in lipodystropy.

Insulin injections

A lipodystrophy can be a lump or small dent in the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

that forms when a person performs injections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those with

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

, using purified

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabol ...

s may also help. One of the side-effects of lipodystrophy is the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma that can cause bleeding that, in turn, will reject the medication. In any of these scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired, thereby allowing the medical condition to worsen. In some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.

Antiretroviral drugs

Lipodystrophy can be a possible side effect of antiretroviral drugs. Other lipodystrophies manifest as

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids incl ...

redistribution, with excess, or lack of, fat in various regions of the body. These include, but are not limited to, having sunken cheeks and/or "humps" on the back or back of the neck (also referred to as buffalo hump) which also exhibits due to excess cortisol. Lipoatrophy is most commonly seen in patients treated with thymidine analogue nucleoside reverse transcriptase inhibitors like zidovudine (AZT) and stavudine (d4T).

Diagnosis

The diagnosis is a clinical diagnosis, established by an experienced endocrinologist. A genetic confirmation may be possible depending on the subtype. In up to ~40% of partial lipodystrophy patients, a causative gene has not been identified. Using a skinfold caliper to measure skinfold thickness in various parts of the body may or a total body composition scan using Dual-energy X-ray Absorptiometry may help identify the subtype. Dual-energy X-ray Absorptiometry may be useful by providing both regional %fat measurements, and direct visualization of fat distribution by means of a "fat shadow".

Treatment

Leptin replacement therapy with human recombinant leptin metreleptin has been shown to be an effective therapy to alleviate the metabolic complications associated with lipodystrophy, and has been approved by the FDA for the treatment of generalized lipodystrophy syndromes. In Europe based on EMA, metreleptin should be used in addition to diet to treat lipodystrophy, where patients have loss of fatty tissue under the skin and build-up of fat elsewhere in the body such as in the liver and muscles. The medicine is used in: adults and children above the age of two years with generalised lipodystrophy ( Berardinelli-Seip syndrome and Lawrence syndrome) and in adults and children above the age of 12 years with partial lipodystrophy (including Barraquer-Simons syndrome), when standard treatments have failed.

Volanesorsen Volanesorsen, sold under the brand name Waylivra, is a hypolipidemic agent, triglyceride-reducing drug. It is a second-generation 2'-''O''-methoxyethyl (2'-MOE) chimeric antisense therapy, antisense therapeutic oligonucleotide (ASO) that targets t ...

is an Apo-CIII inhibitor that is currently being investigated as a potential therapeutic to reduce hypertriglycerides in

Familial Partial Lipodystrophy Familial partial lipodystrophy, also known as Köbberling–Dunnigan syndrome, is a rare genetic metabolic condition characterized by the loss of subcutaneous fat. FPL also refers to a rare metabolic condition in which there is a loss of subcutane ...

patients in the BROADEN study.

Society and culture

Lipodystrophy United
is an American organization founded and run by lipodystrophy patients to support each other and raise awareness about lipodystrophy syndromes.
Lipodystrophy UK
is a dedicated UK charity set up to support people affected by Lipodystrophy. March 31 is observed as the World Lipodystrophy Day.

References

External links

{{Disorders of subcutaneous fat Conditions of the subcutaneous fat