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 (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

. 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 u ...

'' (), 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 Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long ...

which may lead to osteosclerosis. 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 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 syndro ...

Types

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

Pathogenesis

Due to an insufficient capacity of subcutaneous tissue to store fat, fat is deposited in non-adipose tissue ( lipotoxicity), leading to insulin resistance. Patients may display

, 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 (NAFLD) associated with obesity,

levels are very low in lipodystrophy.

Insulin injections

Lipodystrophy can appear as 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 ...

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 mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

, 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 insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

s and new needles with each injection may also help. (Although, in some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.) Some of the side-effects of lipodystrophy are the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma which can cause bleeding that, in turn, causes rejection of 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 condition to worsen.

Antiretroviral drugs

Lipodystrophy can be a possible side effect of certain

antiretroviral drug The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV li ...

s. Lipoatrophy is most commonly seen in patients treated with thymidine analogues and other older HIV drug treatments such as the nucleoside reverse transcriptase inhibitors RTIs like zidovudine (AZT) and stavudine (d4T). Other lipodystrophies manifest as

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

redistribution, with excess, or lack of, fat in various regions of the body. This is often most noticeable in the face. 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 Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

(a so-called "stress" hormone).

Diagnosis

The diagnosis is a clinical one, usually established by an experienced endocrinologist.Using a skinfold caliper to measure skinfold thickness in various parts of the body 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) with Spectral imaging (radiography), spectral imaging. Two X-ray beams, with different energy levels, are aimed at the patient's bones. When soft t ...

may also 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". A genetic confirmation is sometimes possible, depending on the subtype. However, in up to 40% of partial lipodystrophy patients, a causative gene has not been identified.

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 is an Apo-CIII inhibitor that is currently being investigated as a potential therapeutic to reduce levels of hypertriglycerides in Familial Partial Lipodystrophy patients in the BROADEN study.

Epidemiology

Congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

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 infection.

References

External links

{{Disorders of subcutaneous fat Conditions of the subcutaneous fat