Lipodystrophy: Difference between revisions

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'''Lipodystrophy''' syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue.<ref>{{cite journal | vauthors = Phan J, Reue K | title = Lipin, a lipodystrophy and obesity gene | journal = Cell Metabolism | volume = 1 | issue = 1 | pages = 73–83 | date = January 2005 | pmid = 16054046 | doi = 10.1016/j.cmet.2004.12.002 | doi-access = free }}</ref><ref>{{Cite web |url=http://newsroom.ucla.edu/releases/UCLA-VA-Researchers-Discover-Fat-5841 |title=UCLA/VA Researchers discover fat gene |access-date=2017-06-15 |archive-url=https://web.archive.org/web/20181006000925/http://newsroom.ucla.edu/releases/UCLA-VA-Researchers-Discover-Fat-5841 |archive-date=2018-10-06 |url-status=dead }}</ref> The medical condition is characterized by abnormal or degenerative conditions of the body's [[adipose tissue]] ("lipo" is [[Greek language|Greek]] for "fat", and "dystrophy" is Greek for "abnormal or degenerative condition"). A more specific term, ''[[lipoatrophy]]'' ({{ety|el|lipo|fat||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 circulating [[leptin]] which may lead to [[osteosclerosis]]. The absence of fat tissue is associated with [[insulin resistance]], [[hypertriglyceridemia]], [[Non-alcoholic fatty liver disease|non-alcoholic fatty liver disease (NAFLD)]] and [[metabolic syndrome]].<ref name=":0">{{cite journal | vauthors = Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, Mungai L, Oral EA, Patni N, Rother KI, von Schnurbein J, Sorkina E, Stanley T, Vigouroux C, Wabitsch M, Williams R, Yorifuji T | title = The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 101 | issue = 12 | pages = 4500–4511 | date = December 2016 | pmid = 27710244 | pmc = 5155679 | doi = 10.1210/jc.2016-2466 | url = }}</ref><ref name=":1">{{cite journal | vauthors = Ajluni N, Meral R, Neidert AH, Brady GF, Buras E, McKenna B, DiPaola F, Chenevert TL, Horowitz JF, Buggs-Saxton C, Rupani AR, Thomas PE, Tayeh MK, Innis JW, Omary MB, Conjeevaram H, Oral EA | title = Spectrum of disease associated with partial lipodystrophy: lessons from a trial cohort | journal = Clinical Endocrinology | volume = 86 | issue = 5 | pages = 698–707 | date = May 2017 | pmid = 28199729 | pmc = 5395301 | doi = 10.1111/cen.13311 }}</ref>

* Congenital lipodystrophy syndromes

** [[Congenital generalized lipodystrophy]] (Berardinelli-Seip syndrome)

** [[Familial partial lipodystrophy]]

** [[Marfanoid–progeroid–lipodystrophy syndrome]]

** [[CANDLE syndrome|Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome]]<ref>{{cite journal | vauthors = Torrelo A, Patel S, Colmenero I, Gurbindo D, Lendínez F, Hernández A, López-Robledillo JC, Dadban A, Requena L, Paller AS | title = Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome | journal = Journal of the American Academy of Dermatology | volume = 62 | issue = 3 | pages = 489–95 | date = March 2010 | pmid = 20159315 | doi = 10.1016/j.jaad.2009.04.046 }}</ref>

* 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]]

Due to an insufficient capacity of subcutaneous [[adipose tissue|tissue]] to store fat, fat is deposited in non-adipose tissue ([[lipotoxicity]]), leading to [[insulin resistance]].<ref name="pmid31071311" /> Patients may display [[hypertriglyceridemia]], severe [[fatty liver disease]] and little or no adipose tissue.<ref name="pmid31656583">{{cite journal | vauthors=Bruder-Nascimento T, Kress TC, Belin de Chantemele EJ | title=Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function | journal=[[Faculty of 1000#F1000Research|F1000Research]] | volume=8 | pages=F1000 Faculty Rev-1756 | year=2019 | doi = 10.12688/f1000research.20150.1 | pmc = 6798323 | pmid=31656583 | doi-access=free }}</ref> Average patient lifespan is approximately 30 years before death, with liver failure being the usual cause of death.<ref name="pmid31656583" /> In contrast to the high levels seen in [[non-alcoholic fatty liver disease]] (NAFLD) associated with obesity, [[leptin]] levels are very low in lipodystropylipodystrophy.<ref name="pmid31071311" />

A lipodystrophyLipodystrophy can beappear as a lump or small dent in the [[skin]] that forms when a person performs [[Injection (medicine)|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 mellitus|diabetes]], using purified [[insulin]]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.){{cn|date=May 2024}}

OneSome of the side-effects of lipodystrophy isare the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma thatwhich can cause bleeding that, in turn, willcauses rejectrejection 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 medical condition to worsen.{{cn|date=May 2024}}

Lipodystrophy can be a possible side effect of certain [[antiretroviral drug]]s. Lipoatrophy Otheris lipodystrophiesmost manifestcommonly as [[lipid]] redistribution, with excess, or lack of, fatseen in variouspatients regionstreated ofwith thethymidine body. These include, but are not limited to, having sunken cheeksanalogues and/or "humps"other onolder theHIV backdrug ortreatments backsuch ofas the neck (also referred to as buffalo hump)<ref>[http://www.medicinenet.com/script/main/art.asp?articlekey=19678 Physical and Biochemical Changes in HIV Disease] Eric S. Daar, M.D. MedicineNet, Accessed 22 September 2007</ref> which also exhibits due to excess [[cortisol]]. Lipoatrophy is most commonly seen in patients treated with thymidine analogue nucleoside reverse transcriptase inhibitors [NRTIs] <ref>{{cite journal | vauthors = Carr A, Workman C, Smith DE, Hoy J, Hudson J, Doong N, Martin A, Amin J, Freund J, Law M, Cooper DA |date=July title2002 |title= Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial | journal = JAMA | volume = 288 | issue = 2 | pages = 207–15 | date = July 2002 | pmid = 12095385 | doi = 10.1001/jama.288.2.207 |pmid=12095385 |doi-access = free }}</ref> like zidovudine (AZT) and stavudine (d4T).<ref>{{cite journal | vauthors = John M, McKinnon EJ, James IR, Nolan DA, Herrmann SE, Moore CB, White AJ, Mallal SA |date=May title2003 |title= Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients | journal = Journal of Acquired Immune Deficiency Syndromes | volume = 33 | issue = 1 | pages = 29–33 |doi=10.1097/00126334-200305010-00005 date|pmid=12792352 |s2cid=22845453 May|doi-access=free}}</ref> 2003Other |lipodystrophies pmidmanifest =as 12792352[[lipid]] |redistribution, doiwith =excess, 10or lack of, fat in various regions of the body.1097 This is often most noticeable in the face. These include, but are not limited to, having sunken cheeks and/00126334-200305010-00005or |"humps" s2cidon the back or back of the neck (also referred to as buffalo hump)<ref>[http://www.medicinenet.com/script/main/art.asp?articlekey=19678 22845453Physical }}and Biochemical Changes in HIV Disease] Eric S. Daar, M.D. MedicineNet, Accessed 22 September 2007</ref> which also exhibits due to excess [[cortisol]] (a so-called "stress" hormone).

The diagnosis is a clinical diagnosisone, usually 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.<ref name=":0" /> Using a [[Skinfold test|skinfold caliper]] to measure skinfold thickness in various parts of the body may or a [[Dual-energy X-ray absorptiometry#Body composition measurement|total body composition scan]] using [[Dual-energy X-ray absorptiometry|Dual-energy X-ray Absorptiometry]] may also help identify the subtype.<ref name=":1" /><ref>{{cite journal | vauthors = Guillín-Amarelle C, Sánchez-Iglesias S, Castro-Pais A, Rodriguez-Cañete L, Ordóñez-Mayán L, Pazos M, González-Méndez B, Rodríguez-García S, Casanueva FF, Fernández-Marmiesse A, Araújo-Vilar D | title = Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome | journal = Endocrine | volume = 54 | issue = 2 | pages = 411–421 | date = November 2016 | pmid = 27473102 | doi = 10.1007/s12020-016-1002-x | s2cid = 19689303 }}</ref> [[Dual-energy X-ray absorptiometry|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".<ref>{{cite journal | vauthors = Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akıncı B, Horowitz JF, Brown RJ, Oral EA | title = "Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers | journal = Diabetes Care | volume = 41 | issue = 10 | pages = 2255–2258 | date = October 2018 | pmid = 30237235 | pmc = 6150431 | doi = 10.2337/dc18-0978 }}</ref> 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.<ref name=":0" />

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 [[Food and Drug Administration|FDA]] for the treatment of generalized lipodystrophy syndromes.<ref>{{cite journal | vauthors = Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A | title = Leptin-replacement therapy for lipodystrophy | journal = The New England Journal of Medicine | volume = 346 | issue = 8 | pages = 570–8 | date = February 2002 | pmid = 11856796 | doi = 10.1056/NEJMoa012437 | doi-access = free }}</ref> In Europe based on [[European Medicines Agency|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 [[Generalized lipodystrophy|generalised lipodystrophy]] ([[Berardinelli-Seip syndrome]] and [[Acquired generalized lipodystrophy|Lawrence syndrome]]) and in adults and children above the age of 12 years with [[partial lipodystrophy]] (including [[Barraquer–Simons syndrome|Barraquer-Simons syndrome]]), when standard treatments have failed.<ref>{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/myalepta|title=Myalepta {{!}} European Medicines Agency|website=www.ema.europa.eu|date=17 September 2018 |access-date=2019-01-08}}</ref>

[[Volanesorsen]] is an [[Apolipoprotein C3|Apo-CIII]] inhibitor<ref>{{cite journal | vauthors = Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM, Witztum JL | title = Targeting APOC3 in the familial chylomicronemia syndrome | journal = The New England Journal of Medicine | volume = 371 | issue = 23 | pages = 2200–6 | date = December 2014 | pmid = 25470695 | doi = 10.1056/NEJMoa1400284 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, Geary RS, Hughes SG, Viney NJ, Graham MJ, Crooke RM, Witztum JL, Brunzell JD, Kastelein JJ | title = Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia | journal = The New England Journal of Medicine | volume = 373 | issue = 5 | pages = 438–47 | date = July 2015 | pmid = 26222559 | doi = 10.1056/NEJMoa1400283 | s2cid = 205096489 | urldoi-access = https://semanticscholar.org/paper/b8b4f0ae969760d3373ca1d9082abfee85fe16d9free }}</ref> that is currently being investigated as a potential therapeutic to reduce levels of hypertriglycerides in [[Familial partial lipodystrophy|Familial Partial Lipodystrophy]] patients in the BROADEN study.<ref>{{Cite news|url=https://clinicaltrials.gov/ct2/show/NCT02527343|title=The BROADEN Study: A Study of Volanesorsen (Formerly ISIS-APOCIIIRx) in Patients With Familial Partial Lipodystrophy - Full Text View - ClinicalTrials.gov|access-date=2018-03-31|language=en}}</ref>

* [[Keppen–Lubinsky syndrome]]

* [[Lipoedema]]

| DiseasesDB = 30066

| ICD10ICD11 = {{ICD10ICD11|E|88|1|e|70EF01}}, {{ICD11|LD27.6}}

| ICD9 ICD10 = {{ICD9ICD10|272.6E|88|1|e|70}}

| ICDOICD9 = {{ICD9|272.6}}

| OMIMICDO =

| MedlinePlusOMIM = =

| eMedicineSubjMedlinePlus = med =

| eMedicineTopiceMedicineSubj = 1307= med

| eMedicineTopic = 1307
| eMedicine_mult = {{eMedicine2|med|3523}}

| MeshID = D008060