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 Lipoatrophy is the term describing the localized loss of fat tissue. This may occur as a result of subcutaneous injections of insulin in the treatment of diabetes, from the use of human growth hormone or from subcutaneous injections of copaxone us ...

("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 Osteosclerosis is a disorder that is characterized by abnormal hardening of bone and an elevation in bone density. It may predominantly affect the medullary portion and/or cortex of bone. Plain radiographs are a valuable tool for detecting and ...

. The absence of fat tissue is associated with insulin resistance,

hypertriglyceridemia Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and ...

, non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome.

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 Marfanoid–progeroid–lipodystrophy syndrome (MPL), also known as Marfan lipodystrophy syndrome (MFLS) or progeroid fibrillinopathy, is an extremely rare medical condition which manifests as a variety of symptoms including those usually associat ...

** Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome *Acquired lipodystrophy syndromes ** Acquired partial lipodystrophy (Barraquer-Simons syndrome) **

Acquired generalized lipodystrophy Acquired generalized lipodystrophy (also known as "Lawrence syndrome," and "Lawrence–Seip syndrome", abbreviation: AGL) is a rare skin condition that appears during childhood or adolescence, characterized by fat loss affecting large areas of the ...

Centrifugal abdominal lipodystrophy Centrifugal abdominal lipodystrophy is a skin condition characterized by areas of subcutaneous fat loss that slowly enlarge. See also * Lipodystrophy * List of cutaneous conditions * Skin lesion A skin condition, also known as cutaneous con ...

(Lipodystrophia centrifugalis abdominalis infantilis) **

Lipoatrophia annularis Lipoatrophia annularis is a skin condition affecting primarily women, characterized by the loss of subcutaneous fat in the upper extremity.Ferreira-Marques J. Lipoatrophia annularis. Arch Dermatol Syphilis 1953; 195: 479-91. It is a form of lipod ...

(Ferreira-Marques lipoatrophia) ** Localized lipodystrophy **

HIV-associated lipodystrophy HIV-associated lipodystrophy is a condition characterized by loss of subcutaneous fat associated with infection with HIV. Presentation HIV-associated lipodystrophy commonly presents with fat loss in face, buttocks, arms and legs. There is also ...

Epidemiology

Congenital 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 immune ...

infection.

Pathogenesis

Due to an insufficient capacity of subcutaneous

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

lipotoxicity Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. Lip ...

), leading to insulin resistance. Patients display

, severe

fatty liver disease Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complica ...

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 Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...

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 animal coverings, such as the arthropod exoskeleton, have different de ...

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 insulins 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 drug The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multi ...

s. 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 includ ...

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 Dual-energy X-ray absorptiometry (DXA, or DEXA) is a means of measuring bone mineral density (BMD) using spectral imaging. Two X-ray beams, with different energy levels, are aimed at the patient's bones. When soft tissue absorption is subtracted ...

may help identify the subtype.

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 Metreleptin, sold under the brand name Myalept among others, is a synthetic analog of the hormone leptin used to treat various forms of dyslipidemia. It has been approved in Japan for metabolic disorders including lipodystrophy and in the United ...

has been shown to be an effective therapy to alleviate the metabolic complications associated with lipodystrophy, and has been approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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 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