Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue.[1][2] The medical condition is characterized by abnormal or degenerative conditions of the body'sadipose tissue. A more specific term,lipoatrophy (from Greek lipo'fat' and dystrophy'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 circulatingleptin which may lead toosteosclerosis. The absence of fat tissue is associated withinsulin resistance,hypertriglyceridemia,non-alcoholic fatty liver disease (NAFLD) andmetabolic syndrome.[3][4]
Due to an insufficient capacity of subcutaneoustissue to store fat, fat is deposited in non-adipose tissue (lipotoxicity), leading toinsulin resistance.[7] Patients may displayhypertriglyceridemia, severefatty liver disease and little or no adipose tissue.[8] Average patient lifespan is approximately 30 years before death, with liver failure being the usual cause of death.[8] In contrast to the high levels seen innon-alcoholic fatty liver disease (NAFLD) associated with obesity,leptin levels are very low in lipodystrophy.[7]
Lipodystrophy can appear as a lump or small dent in theskin that forms when a person performsinjections repeatedly in the same spot. These types of lipodystrophies are harmless and can be avoided by changing (rotating) the locations of injections. For those withdiabetes, using purifiedinsulins 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.)[citation needed]
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.[citation needed]
Lipodystrophy can be a possible side effect of certainantiretroviral drugs. Lipoatrophy is most commonly seen in patients treated with thymidine analogues and other older HIV drug treatments such as the nucleoside reverse transcriptase inhibitors [NRTIs][9] like zidovudine (AZT) and stavudine (d4T).[10] Other lipodystrophies manifest aslipid 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)[11] which also exhibits due to excesscortisol (a so-called "stress" hormone).
The diagnosis is a clinical one, usually established by an experienced endocrinologist.Using askinfold caliper to measure skinfold thickness in various parts of the body or atotal body composition scan usingDual-energy X-ray Absorptiometry may also help identify the subtype.[4][12]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".[13] 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.[3]
Leptin replacement therapy with human recombinant leptinmetreleptin has been shown to be an effective therapy to alleviate the metabolic complications associated with lipodystrophy, and has been approved by theFDA for the treatment of generalized lipodystrophy syndromes.[14] In Europe based onEMA, 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 withgeneralised lipodystrophy (Berardinelli-Seip syndrome andLawrence syndrome) and in adults and children above the age of 12 years withpartial lipodystrophy (includingBarraquer-Simons syndrome), when standard treatments have failed.[15]
Congenital lipodystrophy (due to inherited genetic defect) is estimated to be extremely rare, possibly affecting only one per million persons.[7] Acquired lipodystrophy is much more common, especially affecting persons withHIV infection.[7]
^James, William D.; Berger, Timothy G.; et al. (2006).Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier.ISBN978-0-7216-2921-6.
^Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendínez F, Hernández A, López-Robledillo JC, Dadban A, Requena L, Paller AS (March 2010). "Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome".Journal of the American Academy of Dermatology.62 (3):489–95.doi:10.1016/j.jaad.2009.04.046.PMID20159315.
