Localized lipodystrophy is usually manifested in the form of isolated or multiple, indentations, particularly in the extremities of the body in childhood. Occasionally, these may disappear all on a sudden. But in some, the lesions may expand. In some cases, secondary pigmentation can be seen on the skin. This form of lipodystrophy is not associated with any underlying disease at the time of presentation. Some patients present with panatrophy of muscle and fat.

Acquired partial lipodystrophy has the onset in childhood usually before 16 years. This is followed by viral infections like measles. Progression of the disease occurs slowly over a period of months to years. One fourth of the patients will have severe fat loss before 13 years of age. Loss of adipose tissue extends from face, neck, and shoulders to upper trunk and abdomen. The lower parts like hips and legs are not usually affected. Metabolic abnormalities are not seen associated with this form. About 60% of the patients may have hepatomegaly.

Extraordinary lack of subcutaneous fat from birth is characteristic of congenital generalized lipodystrophy. Visceral organs are often enlarged and toddlers may have severe pharyngeal tonsils and adenoids. One of the earliest symptoms of this condition include well-defined musculature with prominent superficial veins. Patients may also present with dermatologic manifestations like eruptive xanthomas, hirsutism, and thick, curled scalp hair. Children with this condition may attain more than 90% of adult growth within 10 years.

HIV-associated lipodystrophy is a progressive disease and the severity of symptoms is usually related to age, duration of disease and the duration of use of protease inhibitors or nucleoside reverse transcriptase inhibitors for treatment. It is characterized by an increase in the circumference of the neck, abdominal visceral fat accumulation, and symmetric and asymmetric lipomatoses.

• Infertility

  Some patients may display the features of polycystic ovary syndrome such as hirsutism, oligomenorrhea, polycystic ovaries and infertility. All patients are typically predisposed to early cardiovascular diseases. [orpha.net]

  She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative. [news-medical.net]

  Female patients often become hirsute and may have clitoromegaly, irregular periods, polycystic ovaries, and infertility issues. Other less common clinical features may include mild cognitive deficits and hypertrophic cardiomyopathy. [clinicaladvisor.com]

  Female CGL patients have additional clinical features including hirsutism, clitoromegaly, irregular menstrual periods, polycystic ovaries, and/or infertility 1. [ncbi.nlm.nih.gov]

  Seipin knockout rats have reduced brain weight and infertility with azoospermia [ 17 ]. Some studies have linked seipin defects with motor neuron disease [ 18 ]. [dmsjournal.biomedcentral.com]

• Abdominal Obesity

  Although the effect of this regimen on abdominal obesity, insulin resistance, and hyperlipidemia was profound, no effect on peripheral fat atrophy was seen. [cid.oxfordjournals.org]

  FPLD1 (Köbberling variety; iii and iv) had neck hypertrophy and abdominal obesity. Calf muscle hypertrophy was present in 8 out of 35 patients with FPLDX (23%; 95% CIs 10–40). [doi.org]

  obesity; Breast hypertrophy in women; Increased fat side of the neck; Increased fat back of the neck; Dorsocervical and suprapubic lipomas. [bmjopen.bmj.com]

  Both can present hyperinsulinemia, glucose intolerance, central or abdominal obesity, hypertension, atherogenic lipid profile, hyperuricemia, prothromboticand proinflammatory states [ 123 ]. [intechopen.com]

• Accelerated Growth

  These children usually have a fierce appetite and accelerated growth. In late childhood, acanthosis nigrans develops on large areas of skin. [clinicaladvisor.com]

  During childhood, affected individuals are described as being voracious eaters and may experience accelerated growth. Affected individuals may also experience fatigue. [rarediseases.org]

  Hepatosplenomegaly, umbilical prominence or hernia, acanthosis nigricans, voracious appetite and accelerated growth can occur. Female patients develop hirsutism, may have clitoromegaly, oligomenorrhea and polycystic ovaries. [intechopen.com]

• Asymptomatic

  Asymptomatic impaired glucose tolerance to severe insulin resistance can be noted, and non-alcoholic steatohepatitis and cardiovascular disease are common complications. Any gene in the Partial Lipodystrophy panel can also be ordered individually. [dnatesting.uchicago.edu]

  The number of patients with lactic acidemia (>18 mg/dL [2 mmol/L]) was 13 (26%) in the abacavir group and 11 (20%) in the stavudine/zidovudine group, but lactic acidemia was asymptomatic in all patients and did not require intervention. [doi.org]

  Asymptomatic type 2 diabetes mellitus is diagnosed in 5-10 % of patients [ 126 ]. The new-generation PIs appear to have a milder IR effect and the prevalence of diabetes is lower than described in the early 2000s. [intechopen.com]

• Infectious Mononucleosis

  Causes Often, doctors don't know what causes acquired lipodystrophy, but some triggers are: An infection, such as measles, pneumonia, infectious mononucleosis, or hepatitis A disease where your immune system attacks your body (called an autoimmune disease [webmd.com]

  Infections that have preceded the onset of AGL include varicella, measles, pertussis, diphtheria, pneumonia, osteomyelitis, infectious mononucleosis, and parotitis. [rarediseases.org]

• Splenomegaly

  (See Atlas 2, Part F.) congenital generalized lipodystrophy an autosomal recessive condition marked by the virtual absence of subcutaneous adipose tissue, large body size, splenomegaly, hirsutism, acanthosis nigricans, and reduced glucose tolerance in [medical-dictionary.thefreedictionary.com]

  Severe metabolic complications, along with hepatomegaly and splenomegaly, develop at an early age. Hyperinsulinemia leads to development of widespread acanthosis nigricans, followed by onset of diabetes mellitus during adolescence 7, 8. [ncbi.nlm.nih.gov]

• Pertussis

  Localized lipodystrophy can also be observed in patients having intradermal or subcutaneous injections (eg, insulin, corticosteroids, IM penicillin G, iron dextran, diphtheria/pertussis/tetanus vaccine, acupuncture, recombinant growth hormone). [emedicine.com]

  Infections that have preceded the onset of AGL include varicella, measles, pertussis, diphtheria, pneumonia, osteomyelitis, infectious mononucleosis, and parotitis. [rarediseases.org]

• Overeating

  This leads to over-prominence of the muscles, veins standing out in relief and coarse features suggestive of acromegaly. [news-medical.net]

  On this day, patient organizations from countries and regions all over the world will hold awareness-raising activities. [prnewswire.com]

  "As the death and hospitalization rates from AIDS have rapidly declined over the past decade, due to advanced medications, more people are living with HIV as a chronic illness. [hopkinsmedicine.org]

  Progression of the disease occurs slowly over a period of months to years. One fourth of the patients will have severe fat loss before 13 years of age. Loss of adipose tissue extends from face, neck, and shoulders to upper trunk and abdomen. [symptoma.com]

  METHODS: Intermittent treatment with leptin with follow-up over 5 years. RESULTS: Pretreatment metabolic abnormalities included insulin resistance, hypertriglyceridemia and steatohepatitis. Leptin was started at the age of 10 years. [ncbi.nlm.nih.gov]

• Abdominal Pain

  We report a case of a 35-year-old male who was admitted to our hospital with a history of abdominal pain, constipation and a palpable mass in the left lower quadrant. [ncbi.nlm.nih.gov]

  Advanced Search: • Use “ “ for phrases o [ “pediatric abdominal pain” ] • Use – to remove results with certain terms o [ “abdominal pain” –pediatric ] • Use OR to account for alternate terms o [teenager OR adolescent ] [msdmanuals.com]

  The only side effects reported were abdominal pain, low blood sugar (hypoglycemia), headache, and decreased weight. [medicaldaily.com]

  ADVERSE REACTIONS: Most common adverse reactions (≥10%) in clinical trials were headache, hypoglycemia, decreased weight, and abdominal pain. [myaleptpro.com]

  High triglyceride levels can sometimes cause pancreatitis, an inflammation of the pancreas that can cause severe abdominal pain and vomiting. There are multiple types of acquired lipodystrophy. [chop.edu]

• Increased Appetite

  Increase In Appetite In CGL, AGL, and FPL, many patients have markedly increased appetites (Hyperphagia – Pages 110 & 114). [lipodystrophyunited.org]

  They have low levels of circulating leptin, which may contribute to their increased appetite. Females with congenital lipoatrophy may exhibit clitoromegaly, hirsutism, or both at birth. The hirsutism usually increases with age. [emedicine.com]

  Appetite Stimulants: Megace (megestrol acetate) Approved by U.S. [poz.com]

  Together with other mechanisms (hypoleptinemia, insulin resistance, etc.), low body fat would explain the increased appetite commonly seen in these patients. [dmsjournal.biomedcentral.com]

• Eating Frequently

  They may consume large amounts of food (similar to patients with bulimia) and may have the urge to eat frequently. They have low levels of circulating leptin, which may contribute to their increased appetite. [emedicine.com]

• Abdominal Distension

  Acromegaloid facies, prognathism, atrophic cheeks, abdominal distension (female) Fig. 2 a Abdominal distension (hepatomegaly), umbilical protrusion, and phlebomegaly b in two patients with Berardinelli-Seip syndrome Laboratory investigations Biochemistry [dmsjournal.biomedcentral.com]

• Hypertension

  We report a case of secondary membranous lipodystrophy associated with both hypertension and venous insufficiency. [ncbi.nlm.nih.gov]

  Hypertension presents next, although this is more variable. Finally, fasting hyperglycemia—frank diabetes—occurs many years later and most likely reflects pancreatic β-cell failure in the context of chronic insulin resistance. [circ.ahajournals.org]

  Metabolic abnormalities including insulin resistance, high blood pressure (hypertension), and severe hypertriglyceridemia have also been reported. This form of FPL has only been reported in women. [rarediseases.org]

• Hepatomegaly

  Severe dyslipideaemia, hepatomegaly and non-alcoholic steatoheaptitis are almost always noted. [dnatesting.uchicago.edu]

  […] and buttocks. total lipodystrophy an autosomal recessive disorder occurring mainly in females, characterized by a generalized loss of subcutaneous fat and extracutaneous adipose tissue, present at birth or appearing later in life, and associated with hepatomegaly [medical-dictionary.thefreedictionary.com]

  An enlarged liver (hepatomegaly) is also common. Hepatomegaly is caused by the accumulation of fat in the liver (fatty liver or steatosis). [rarediseases.org]

  These patients often present with low height and weight, developmental delays, enlarged livers (hepatomegaly) and often have chronic anemia, elevated liver enzymes and elevated acute phase reactants on lab tests. [autoinflammatory.org]

• Hepatosplenomegaly

  The babies may have an umbilical protrudence or hernia and hepatosplenomegaly. A few patients develop diabetes in infancy, but most become diabetic during adolescence or later. These children usually have a fierce appetite and accelerated growth. [clinicaladvisor.com]

  Other features include severe acanthosis nigricans, hepatosplenomegaly, and the development of metabolic complications like diabetes early in life. The condition is caused by a mutation of the AGPAT2 or seipin genes. [news-medical.net]

  Affected subjects have extreme paucity of adipose tissue from birth, leading to a muscular appearance with prominent veins and an acromegaloid appearance, along with severe acanthosis nigricans, hepatosplenomegaly, and early onset of diabetes, hypertriglyceridemia [mayoclinic.org]

  […] function. 2 Patients with this syndrome have plasma triglyceride levels ranging from 10 to 100 times the normal value (1500 to 15,000 mg per deciliter [17 to 170 mmol per liter]), eruptive xanthomas, arthralgias, neurologic symptoms, lipemia retinalis, and hepatosplenomegaly [doi.org]

• Advanced Bone Age

  Advanced bone age and linear growth and skeletal muscle prominence can be seen during childhood. Severe dyslipideaemia, hepatomegaly and non-alcoholic steatoheaptitis are almost always noted. [dnatesting.uchicago.edu]

  bone age, acanthosis nigricans and hirsutism. lip·o·dys·tro·phy ( lip'ō-dis'trō-fē ), 1. [medical-dictionary.thefreedictionary.com]

  Patients with CGL can develop hyperphagia as a result of profound leptin deficiency in early childhood, and may have accelerated linear growth, advanced bone age and features suggestive of acromegaly such as enlarged hands, feet and jaw 5, 6. [ncbi.nlm.nih.gov]

• Large Hand

  Adults may have large hands and feet and a strong, square jawbone if their hormone balance is off and they've kept growing. They could have larger than usual sex organs (clitoris and ovaries, penis and testicles). [webmd.com]

  Patients with the early-onset hyperinsulinemia in combination with congenital generalized lipoatrophy develop acromegaloid features (large hands, feet, and jaw) with soft tissue hyperplasia, somatomegaly, and bony abnormalities. [emedicine.com]

• Hirsutism

  (See Atlas 2, Part F.) congenital generalized lipodystrophy an autosomal recessive condition marked by the virtual absence of subcutaneous adipose tissue, large body size, splenomegaly, hirsutism, acanthosis nigricans, and reduced glucose tolerance in [medical-dictionary.thefreedictionary.com]

  Diabetes, hypertriglyceridemia, hypertension, fatty liver, pancreatitis, and hirsutism have also been reported. Metabolic abnormalities are more prominent than the lipodystrophy in this form of the disorder. [rarediseases.org]

  A quarter of affected women have hirsutism and irregular periods, possibly reflecting polycystic ovarian syndrome. The acquired lipodystrophies are mainly autoimmune in origin and display complement abnormalities. [clinicaladvisor.com]

  Some patients may display the features of polycystic ovary syndrome such as hirsutism, oligomenorrhea, polycystic ovaries and infertility. All patients are typically predisposed to early cardiovascular diseases. [orpha.net]

• Absence of Subcutaneous Fat

  […] lipodystrophy [ lip″o-dis´tro-fe ] 1. any disturbance of fat metabolism. 2. a group of conditions due to defective metabolism of fat, resulting in absence of subcutaneous fat; they may be congenital or acquired and partial or total. [medical-dictionary.thefreedictionary.com]

  […] of subcutaneous fat. [care.diabetesjournals.org]

  FPLD2 (Dunnigan variety; i and ii) typically presents with the same signature phenotype with absence of subcutaneous fat in the extremities, hips, and abdomen (flanks), along with a hypertrophy in the neck, axillae, and mons pubis. [doi.org]

  Transverse sections of the midthigh demonstrate asymmetrical absence of subcutaneous fat, with preservation of medial subcutaneous fat and marrow fat (bottom left). [emedicine.com]

• Subcutaneous Nodule

  / trunk chest / abdomen Age: 38 years Contributor: Scott Crater Description: lipoatrophy and violaceous subcutaneous nodules Comments: This 38 year old man developed recurrent subcutaneous nodules on the trunk and proximal extremities, accompanied by [web.archive.org]

  New nodules appear and there is progression of subcutaneous fat loss. Autoimmune disease variety (type 2): In this variety, the patients have past or present evidence of autoimmune diseases. [lipodystrophyunited.org]

  Lupus erythematosus panniculitis is a rare disease characterized by deep subcutaneous nodules, most commonly localized on the upper limbs and face. [sclero.org]

  Lipodystrophy in panniculitis-associated AGL is preceded by the development of painful subcutaneous nodules or lesions consisting of small spots or bumps (maculopapular lesions). [rarediseases.org]

• Xanthoma

  Patients may also present with dermatologic manifestations like eruptive xanthomas, hirsutism, and thick, curled scalp hair. Children with this condition may attain more than 90% of adult growth within 10 years. [symptoma.com]

  […] mutations in genes encoding other proteins necessary for LPL function. 2 Patients with this syndrome have plasma triglyceride levels ranging from 10 to 100 times the normal value (1500 to 15,000 mg per deciliter [17 to 170 mmol per liter]), eruptive xanthomas [doi.org]

  Eruptive xanthomas are not frequent. In the literature, there are several reports of umbilical hernia in patients with BSCL [ 12, 22 ]. [dmsjournal.biomedcentral.com]

  Other common clinical manifestations include polycystic ovarian syndrome (PCOS), acanthosis nigricans as a result of severe insulin resistance, and eruptive xanthomas due to extreme hypertriglyceridemia 1 – 3. [ncbi.nlm.nih.gov]

  The musculature is typically well-defined with prominent superficial veins due to the paucity of adipose tissue. [18] Severe hypertriglyceridemia may be present early on and result in eruptive xanthomas and recurrent pancreatitis. [emedicine.com]

• Hypertrichosis

  […] emaciation and progressing downward, giving an apparent and possibly real accumulation of fat about the thighs and buttocks. total lipodystrophy a recessive condition marked by the virtual absence of subcutaneous adipose tissue, macrosomia, visceromegaly, hypertrichosis [medical-dictionary.thefreedictionary.com]

  It results in gigantism ( acromegaly ), enlarged liver and kidneys, pancreatitis, acanthosis nigricans and increased body hair (hypertrichosis) as well as generalised loss of body fat. [dermnetnz.org]

• Hunger

  Behavioral tests demonstrated that perceived hunger, importance of eating, eating frequencies, and liking ratings of food pictures significantly decreased during metreleptin therapy. [ncbi.nlm.nih.gov]

  Tell your doctor right away if you experience shakiness, sweating, headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, or a jittery feeling because these may be signs of low blood sugar (hypoglycemia). [myalept.com]

  So increasing leptin levels should halt hunger– but it wasn’t so simple. Injections of leptin helped only the handful of people who can’t make the hormone. [blogs.plos.org]

• Clitoromegaly

  Female patients often become hirsute and may have clitoromegaly, irregular periods, polycystic ovaries, and infertility issues. Other less common clinical features may include mild cognitive deficits and hypertrophic cardiomyopathy. [clinicaladvisor.com]

  Female CGL patients have additional clinical features including hirsutism, clitoromegaly, irregular menstrual periods, polycystic ovaries, and/or infertility 1. [ncbi.nlm.nih.gov]

  Female patients develop hirsutism, may have clitoromegaly, oligomenorrhea and polycystic ovaries. [intechopen.com]

  Females with congenital lipoatrophy may exhibit clitoromegaly, hirsutism, or both at birth. The hirsutism usually increases with age. Reproductive abnormalities are common. [emedicine.com]

• Kidney Failure

  Depending on which type of lipodystrophy a person has, it may cause other problems, including diabetes, high cholesterol and triglycerides, liver disease, and kidney failure. Doctors can help you manage these complications. [webmd.com]

• Amenorrhea

  Some women have hypogonadotropic amenorrhea, probably due to leptin deficiency. [emedicine.com]

Diagnosis of this disease is mainly based on clinical features. Laboratory studies are used to check for associated conditions like metabolic disorders, and autoimmune diseases. In many cases histopathological studies are the confirmatory diagnostic test. Histology depends on the type of lipodystrophy. The two main histopathological subsets are involutional type and inflammatory type. In involutional type small lipocytes are seen embedded in hyaline connective tissue, lobular accentuation in the periphery, and scarcity of inflammatory cells. In inflammatory type, normal lipocytes and vasculature are present. Focal lymphocytes, histiocytes and plasma cells are scattered. These forms are more commonly seen in localized lipodystrophy.

To rule out associated disorders, tests including fasting blood glucose and lipid profile, creatinine, and urinalysis may be useful. Tests may also be conducted for antinuclear antibodies, and anticardiolipin antibodies. For familial form of lipodystrophy, genetic workup may be needed. In progressive lipodystrophy, immunofluorescence studies may be helpful.

• Enlargement of the Liver

  There may be abnormal breakdown of fats with loss of weight, excessive levels of fats in the blood, raised blood sugar levels, enlargement of the liver and abnormal thyroid gland function. [medical-dictionary.thefreedictionary.com]

  This condition results in enlargement of the liver and kidneys. [epainassist.com]

  These patients often present with low height and weight, developmental delays, enlarged livers (hepatomegaly) and often have chronic anemia, elevated liver enzymes and elevated acute phase reactants on lab tests. [autoinflammatory.org]

  Some individuals develop abnormal enlargement of the liver (hepatomegaly) due to the infiltration and accumulation of fat within the liver. This can be known as hepatic steatosis or fatty liver. [rarediseases.org]

• Hypertriglyceridemia

  However, the role of apoCIII in hypertriglyceridemia in lipodystrophy and the effects of leptin replacement on apoCIII levels are unknown. [ncbi.nlm.nih.gov]

  Insulin resistance, severe hypertriglyceridemia, and diabetes were also reported. [rarediseases.org]

  These mice exhibited diabetes, hypertriglyceridemia, and hepatic steatosis in addition to severe leptin deficiency. [emedicine.com]

• VLDL Increased

  Ann Rev Genomics Human Genet 2006; 7: 175-199] Various mechanisms involved in ART-related dyslipidemia have been described: reduction in the catabolism of VLDL, increased VLDL production, impaired catabolism of FFA, increased liver triglyceride synthesis [intechopen.com]

• Leptin Decreased

  The effects of leptin-replacement therapy appeared to be independent of the decrease in food intake. [doi.org]

Just like the different types of the disease, the treatment options are also varied. Efficacy of the treatment modality also depends on the type of the disease and the clinical features in an individual. Generally, any treatment strategy focus on alleviating the metabolic and pathologic changes in the distribution of fat. A general approach includes lifestyle modification like diet, exercise, and nutritional therapy. Patients with this disease are recommended to have less than 30% of daily calories from fat. About 60-70% of the calories should be provided by monounsaturated fat and carbohydrates. Exercise may be helpful in improving the metabolic parameters. Resistance training is found to enhance total lean mass and to decrease total fat accumulation. Exercise is also helpful in increasing peripheral insulin sensitivity, and HDL cholesterol levels.

Patients with concurrent diabetes may be suggested metformin for managing associated condition. Thiazolidinediones also may be helpful in improving insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Treatment guidelines for dyslipidemia in lipodystrophy is similar to that of coronary artery disease. Lifestyle modification is the first step in this regard. Statins are given for hypercholesterolemia. Fibrates and extended release niacin may be used for controlling hypertriglyceridemia. Ezetimibe inhibitors may be opted for patients who cannot tolerate statins.

Mortality and morbidity associated with the disease depends on the organ involved and the extent of involvement. If no other organ systems are involved, prognosis of lipodystrophy is good. Most of the patients will have a normal life expectancy without many disabilities. Even a progressive form of the disease like acquired partial lipodystrophy has a good prognosis if associated complications like renal impairment and insulin resistance are absent. In congenital forms most of the patients survive to young adulthood or early middle age.

Most forms of localized lipodystrophy have idiopathic etiology. Occasionally it is seen associated with subcutaneous and intradermal injections. Trauma at the site of injection is implicated in the release of cytokines that enhance catabolism of fat. Contamination of animal insulin is also found to cause localized lipodystrophy by cross reaction with lipid tissues and insulin antibody. This form of lipid dystrophy is very rare compared to other forms [4]. Similarly, no special etiology is known for partial dystrophy also. There are reports of progressive partial lipodystrophy being associated with a history of viral or bacterial infection.

Inherited forms of lipodystrophy are caused by mutations. Congenital generalized lipodystrophy (CGL), characterized by total absence of adipose tissue, is caused by an autosomal recessive mutation. There are four subtypes of CGL, caused by compound mutations in four genes, 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT2), Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), caveolin 1 (CAV1), and polymerase I and transcript release factor (PTRF).

The incidence and prevalence of many forms of lipodystrophy are not known. Both acquired and inherited forms of this disease are rare. Localized lipodystrophies, including the cases secondary to injections are rare. Few of them are reported in literature. Information on racial association of the disease is lacking. In general, females are found to be more affected than males in case of localized lipodystrophy. Onset of this form usually occurs within 10 to 20 years of age, and may be present from infancy to adulthood.

Acquired partial lipodystrophy is more common than generalized form of the disease. A total of 250 cases have been reported in United States [5]. As in the case of localized lipodystrophy, no specific association has been reported between race and occurrence of acquired lipodystrophy. The prevalence is found to be four times more among women when compared to men. The median age of onset for acquired partial lipodystrophy is around 7 years, and occasionally it is also noted in 40 to 50 years. The clinical manifestations are found to start at a later stage in women when compared to men. The estimated prevalence of this form of inherited lipodystrophy is around 1 in 15 million persons.

Incidence of congenital lipodystrophy is found to be equal in male and female. Highest frequency of congenital generalized lipodystrophy is reported from Brazil [6]. Congenital generalized lipodystrophy is a rare autosomal recessive disorder and around 250 cases are reported world over in literature. No difference has been reported in the frequency of this disorder in different parts of the world [7].

Congenital generalized lipodystrophy is classified into type 1 to 4, depending on the clinical manifestations and the etiological mutations. Type 1 (CGL1) is caused by a mutation of 1-acylglycerol-3-phosphate-O-acyltransferase 2 gene (AGPAT2). AGPAT2 gene plays an important role in functioning of adipocyte tissue and also in the synthesis of triacylglycerol in adipose tissue [8]. Mutation of this gene affects the metabolically important tissue like the fat tissue in subcutaneous region, bone marrow, intramuscular, intraabdominal and intrathoracic regions. Type 2 (CGL2) occurs due to mutations of Berardinelli-Seip Congenital Lipodystrophy 2 gene (BSCL2). BSCL2 gene is involved in the coding of the protein seipen, which is implicated in the differentiation of adipose tissue and lipid droplet formation [9]. Caveolin 1 (CAV1) mutations, and Polymerase I and transcript release factor (PTRF) mutations are associated with CGL3, and CGL4, respectively.

Many genetic mutations have been implicated in the development of inherited partial lipodystrophy. The most prevalent form is familial partial lipodystrophy type 2 and is caused by a mutation in the gene LMNA [10]. HAART-associated lipodystrophy syndrome is a side-effect of HAART. Lipodystrophy may be caused by nucleoside reverse transcriptase inhibitors. It may result in abnormal proliferation of mitochondria, known as mitochondrial toxicity [10]. Protease inhibitors are also implicated in the disruption of adipocyte differentiation and also in increased production of cytokines. Drug-induced lipodystrophy may also include increased lipolysis. Enhanced lipolysis along with deficiency of subcutaneous fat, indirectly lead to metabolic disturbances like insulin resistance and dyslipidemia.

No known method of prevention exist for lipodystrophy. In most of the cases controlling the underlying condition would go a long way in preventing complications.

Lipodystrophy is a disorder characterized by atrophy of adipose tissue which may be localized, partial, or total, depending on the location and degree of fat loss [1]. Total lipodystrophy can be congenital with complete loss of fat tissue in the body and is often associated with metabolic abnormalities like insulin resistance, hyperlipidemia, and hyperglycemia. Partial lipodystrophy is manifested by loss of adipose tissue, particularly from face. Similar atrophy may not be present in other parts of the body. Localized lipodystrophy is manifested by localized loss of fat tissue.

Complications of lipodystrophy are often associated with the extent of loss of adipose tissue [2]. Loss of adipose tissue occurs from the subcutaneous region and sometimes from visceral region [3]. Lipodystrophy disorders result in fat redistribution, including lipohypertrophy and lipoatrophy. These disorders may lead to cosmetic problems in some, while in others it may even lead to severe metabolic complications. Lipodystrophy may be inherited or secondary to other illnesses, called as acquired lipodystrophy.

Lipodystrophy refers to a heterogeneous group of disorders that result in fat loss. As more and more of fat is lost from the body, other organs and structures underneath the skin become more defined and fat loss may be noted as depressions on the skin. Lipodystrophy may be categorized as congenital or acquired. It may also be divided as generalized, where fat loss occurs all over the body, and partial where fat loss occurs only in some parts of the body. Loss of fat leads to metabolic complications, the severity of which depends on the extent of loss.

Location of fat loss may vary from one person to another. Some patients may have very thin face and arms, while others may have very less fat on the lower areas of the body like legs and buttocks. Some others may have very little fat and appear muscular. In most of these patients, fat may be present in unusual places like kidney, blood, heart, liver and pancreas. This may lead to serious problems like insulin resistance, high cholesterol, diabetes mellitus, fatty liver disease and heart disease.

Clinical features with a family history of lipodystrophy and associated conditions are often used in diagnosis of the disease. Associated conditions may include diabetes mellitus, high levels of triglycerides or cholesterol, fatty liver, dark, velvety patches of skin and polycystic ovary syndrome. Treatment strategy include alleviating the disturbances due to changes in fat distribution. Lifestyle modifications with diet, nutrition therapy and exercise are important steps in the treatment of the condition. Medications are given for controlling diabetes mellitus, high levels of cholesterol and triglycerides. If no organs are involved in the disease, lipodystrophy has a good prognosis.

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