Acta Pharmacologica Sinica (2012) 33: 155–172
© 2012 CPS and SIMM All rights reserved 1671-4083/12 $32.00
Lifestyle-induced obesity in children and adults has reached
epidemic proportions worldwide. In the United States (US),
a third of adults aged 20 years and over are overweight, a
third are obese, and over five percent are extremely obese.
The National Health and Nutrition Examination Survey and
Pediatric Nutrition Surveillance System reported a tripling
of the prevalence of obesity among US school-age children
and adolescents over the past three decades. Numerous
published studies validate the weight loss efficacy of lifestyle
changes that include decreased amounts and types of food,
and improved exercise regimens. Medications used for the
treatment of obesity are severely limited[3, 4]. Bariatric surgery
has been exceptional in its ability to induce weight loss and
resolve the co-morbidities of obesity, though complications
rates can be high, many people are still obese by body mass
index (BMI) after Roux-en-Y gastric bypass (RYGB), and
weight regain occurs[7, 8].
This review aims to demonstrate lymphatic dysfunction as a
component of rare adipose disorders (RADs) that increases the
amount and alters the location of subcutaneous adipose tissue
(SAT) while resisting fat loss after lifestyle changes or bariatric
surgery. Lipodystrophies are also discussed as they may be
confused with rare adipose disorders (RADs).
Non-lifestyle causes of obesity
Lipodystrophies or fat redistribution syndromes involve a
primary lack or loss of SAT; however, increased SAT in other
areas can be confused with lifestyle-induced obesity. Human
immunodeficiency virus (HIV)-associated lipodystrophy, is
well-known, but familial partial lipodystrophies are rare and
therefore less well known, and can go undiagnosed for years
or are never recognized. Acquired partial lipodystrophy, also
rare, with a progressive and symmetrical lipoatrophy of SAT
starting from the face and spreading to the upper part of the
body, sparing the legs, can be confused with the RAD, lipe-
dema, due to a disproportion between upper and lower body
SAT (see below).
Human immunodeficiency virus (HIV)-associated lipodystrophy
HIV-and highly active antiretroviral treatment (HAART)-
associated lipodystrophy includes loss of SAT from the face,
Rare adipose disorders (RADs) masquerading as
Karen L HERBST
Department of Medicine, University of California, San Diego and Veteran’s Affairs San Diego Healthcare System, USA
Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum’s disease (DD) may be misdi-
agnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity.
Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely
reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell popula-
tion with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with
RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart
from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystro-
phies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-
based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD
conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment
regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve
quality of life and construct advanced treatment regimens for future generations.
Keywords: adiposis dolorosa; Dercum’s disease; lipedema; multiple symmetric lipomatosis; familial multiple lipomatosis; familial par-
tial lipodystrophy; lymph; lymphatics
Acta Pharmacologica Sinica (2012) 33: 155–172; doi: 10.1038/aps.2011.153
* To whom correspondence should be addressed.
Received 2011-08-31 Accepted 2011-10-12
Acta Pharmacologica Sinica
buttocks, arms, and legs. In men with lipodystrophy, SAT
can be increased on the abdomen and chest (gynecomastia),
and a dorsocervical fat pad or “buffalo hump” is common[9, 10].
The SAT in the dorsocervical fat pad is thought to be identi-
cal to the SAT in multiple symmetric lipomatosis (MSL), one
of the RADs (see below). Upper body fat, including parotid
hypertrophy, circumferential enlargement of the neck and a
dorsocervical fat pad are associated with insulin resistance
in HIV+ men[11–13] as is intermuscular fat and SAT on the legs
in HIV+ women. Large breasts are part of HIV lipodystro-
phy in Black women and other non-Caucasian ethnicities.
Women with HIV may also develop increased SAT on the
upper part of the arm out of context with the usual lipoatro-
phy in this area in HIV+ men suggesting an estrogen and/or
progesterone component to location of the SAT. This upper
arm SAT looks visually similar to the SAT in women with the
RAD, MSL (see below and Figure 1). In addition to excision
of excess SAT as treatment for lipodystrophy, tesamorelin,
a synthetic analogue of human growth hormone-releasing
hormone, is FDA-approved for the reduction of excess visceral
adipose tissue in HIV-infected patients with lipodystrophy.
Visceral adipose tissue was reduced up to 18% during active
use of tesamorelin. The glucagon-like peptide-1 agonist,
exenetide, also improved the HIV- and treatment-induced
obesity through weight loss in a single case.
Acquired partial lipodystrophy (APL; BARRAQUER-SIMONS
Acquired partial lipodystrophy is characterized by a regional
loss of SAT primarily in children and adolescents starting at
the face and extending to the waist, sparing the legs; in fact
SAT may be increased on the legs. Because of the higher
amount of SAT in the legs compared to the upper body, APL
could be confused with the RAD, lipedema (Figure 2). In lipe-
dema, there is increased fat on the legs but the fat of the upper
body is normal or increased (see below). APL is thought to
be autoimmune occurring after a febrile (viral) illness with
Figure 1. Multiple symmetric lipomatosis
with or without HIV infection. A and B, non-
HIV-related MSL Type II; note increased upper
arm size and increased fat on back. Not
shown is increased fat in the labia majora.
C and D, increased arm and back fat,
respectively in HIV-and HAART-induced MSL
Type II. Arrows point to end of MSL fat on the
upper arm. Normal labia majora (not shown).
Figure 2. Acquired partial lipodystrophy and lipedema. A, a 37 year old
woman with acquired partial lipodystrophy. C3 level<16.1 mg/dL (normal
range: 90-180) and C4 level 23.11 mg/dL (normal range: 10-40). Note the
loss of SAT from the upper body to the waist but obesity of the hips and
legs (photo by Dr Alper GuRLEK). B, a woman with lipedema stage II and
a previous history of obesity with a 100 kg weight loss; note redundant
skin on arms and abdomen from weight loss of non-RAD fat; note also
lipedema in legs.
Acta Pharmacologica Sinica
low levels of complement factor 3 (C3) and the presence of a
circulating autoantibody called complement 3-nephritic factor.
Treatment with the thiazolidinedione, rosiglitazone, improved
levels of C3 and increased SAT in a participant with APL.
Familial partial lipodystrophies (FPLD)
FPLD Type 1: FPLD1, also known as Köbberling lipodystro-
phy, is a lesser known partial lipodystrophy primarily found
in women causing a lipodystrophy of the arms, legs, and
sometimes breasts, with an increase in fat on the abdomen and
remainder of the trunk. The prevalence of FPLD1 and any
genetic mutation remains unknown. There are no blood or
urine biomarkers for FPLD1. FPLD1 may go unrecognized if
the practitioner does not recognize the lipodystrophy; finding
a ledge where SAT ends on the buttocks can help in the diag-
nosis. Diabetes and hypertriglyceridemia are highly prevalent
in FPLD1 while acanthosis nigricans is minimal. Treatment is
restricted to usual care of obesity-associated co-morbidities,
although, RYGBP should be considered as it improved weight
and co-morbidities in a case of FPLD1.
FPLD Type 2: The best studied FPLD is Type 2 (FPLD2),
also known as Dunnigan lipodystrophy. In FPLD2, SAT is
lost around the time of puberty from the legs, arms, buttocks,
abdomen and chest; areas of remaining SAT deposits are on
the back, face and chin, giving a Cushingoid appearance; fat
is increased in the labia majora in women; this finding also
occurs in women with MSL (Figure 1). Mutations in the lamin
A and C gene, LMNA, cause FPLD2. People with FPLD2
have all the co-morbidities associated with obesity. Leptin
levels can be very low in lipodystrophies and leptin treatment
has shown benefit but remains investigational. RYGB has
also shown benefit in reducing the co-morbidities associated
FPLD Type 3: Mutations in the peroxisome proliferator-
activated receptor gamma (PPARG) gene can cause partial
lipodystrophy with abdominal obesity known as FPLD3;
people with FPLD3 may look very similar to FPLD2. Treat-
ment with thiazolidinediones may be useful in people with
PPARG gene mutations and other cases of FPLD without
identified gene mutations.
Additional lipodystrophies and single cases of additional
types of FPLD have been well reviewed.
Multiple Symmetric Lipomatosis (Madelung’s disease/syndrome;
Launois Bensaude syndrome)
Multiple symmetric lipomatosis (MSL) is a rare syndrome
(Table 1) originally described in 1846, characterized by the
painless, symmetrical accumulation of abnormal tumor-like
SAT. The first systematic treatise was by the German surgeon
Dr Otto Madelung who collected 30 cases and reported an
additional 3 cases in 1888 under the name “Fetthals” or fat
neck, but the French Physicians Drs Pierre-Emile LAUNOIS
and Raoul BENSAUDE gave prominence to and caused rec-
ognition of MSL by publishing a detailed account of 65 cases
in 1898. There are many synonyms for MSL including
benign symmetric lipomatosis but this disorder is anything
but benign, arguing against its use. Over 300 adult cases are
reported in the literature with an age range of 20–71 years.
The early literature on MSL was dominated by research on
alcoholic men with a reported incidence of 1/25 000 in the
Italian population. Non-alcoholics and women are also
affected[36–38]; two cases have been reported in children[39, 40].
Identification of MSL is by history and clinical exam. There
are no blood or urine biomarkers for MSL and the gene(s)
remains unknown in a majority of cases. Individuals with
MSL have increased SAT, either as discrete non-encapsulated
lipomas or as a confluent increase in SAT in a symmetrical dis-
tribution on the neck, the back, the chest, the upper arms, or
on the thighs; MSL usually spares the distal limbs but not in
many women with MSL where the altered fat may be global
(Figure 3). Because the appearance and location of SAT in
MSL can vary, MSL has been divided into three types:
Clinical types of MSL[37, 43]
Type I, head and/or neck with extension down the back,
or only on the back: In rare cases, MSL SAT can invade the
lingual muscles of the tongue[44, 45], or the vocal cords and
compress the recurrent laryngeal nerve causing hoarseness,
or increase periorbital fat. Tracheal or esophageal compres-
sion and the superior vena cava syndrome can be found in
15%–20% of patients. The presence of a dorsocervical fat
pad (buffalo hump) can be found both in MSL[41, 49, 50] and HIV-
associated lipodystrophy[9, 10, 51, 52]; it has been proposed that
the fat in these two disorders arises from brown adipose tissue
located in that area.
Type II body: Includes the shoulder girdle, the upper arms,
the thorax, the back, the abdomen and upper buttocks. In one
case, fat grew around the testicles in the scrotum and was con-
tiguous with MSL tissue in the perineum and the root of the
penis. Also rare is growth of the MSL fat on the hands.
Table 1. Identifying codes or numbers for SAT Disorders.
Code or number
Listed by NORD
NLM MESH ID
Chronic pain Lymphedema, not
ICD=International Classification of Diseases; MESH=medical subject
headings; NLM=national Library of Medicine; NORD=National
Organization of Rare Disease; OMIM=Online Mendelian Inheritance in
Man; *Application for a MESH code submitted
Acta Pharmacologica Sinica
Many individuals have a combination of Types II and III.
While the MSL fat grows, normal fat and muscle can undergo
wasting which can be confused with a partial lipodystrophy
Type III, thigh (female type): Rarest type. MSL type III is
clinically similar to and may be instead, the RAD, lipedema
(see below). Women tend to have Type II and III MSL with
widespread altered SAT.
MSL is thought to be inherited through mitochondrial muta-
tions in a few familial cases including multiple deletions of
mitochondrial DNA, and the myoclonus epilepsy and ragged-
red fibers (MERRF) tRNA(Lys) A>G(8344) mutation[56, 57].
Klopstock et al found mitochondrial mutations in only 2 of
12 patients studied. Chalk et al found no mitochondrial
pathology or mutations in four siblings with MSL with a pat-
tern favoring autosomal recessive. The phenotype of MSL
may require a combined effect of alcohol (or other insult) and
a currently unknown genetic mutation.
Histology of MSL fat
Individual fat cells have been described as smaller than
normal[38, 49, 59] or normal sized. MSL SAT is thought to be
derived from brown adipose tissue (BAT) or as white adi-
pose tissue (WAT) that transdifferentiates into BAT[49, 60, 61].
Ultrastructurally, brown adipocytes have numerous large
mitochondria packed with cristae. Under light microscopy,
brown adipocytes have cytoplasmic lipids arranged as numer-
ous small droplets (multilocularity), while white adipocytes
have cytoplasmic lipids arranged in a unique vacuole (uni-
locularity). In BAT, the metabolic reactions of mitochondria
are uncoupled from ATP synthesis by uncoupling protein
(UCP)-1 so that energy produced is released as heat. Infants
and even adolescents have a substantial amount of BAT, espe-
cially between the shoulder blades. BAT persists throughout
adulthood in the perirenal, omental, mesenteric, pericardial,
intercostal, axillary, cervical, and interscapular fat, embedded
within WAT[63, 64] with an approximated ratio of 1 brown adi-
pocyte for every 200 white adipocytes[65, 66].
By light microscopy, adipocytes in MSL SAT are monovacu-
olar[67, 68] or multivacuolar. By electron microscopy of long-
term primary cultures from the stromal vascular fraction
(SVF), containing stem and immune cells, cells were polymor-
phic with thin microfilaments suggestive of elevated metabolic
activity, were multivacuolar, and had large mitochondria
packed with cristae suggesting a more BAT phenotype in
Physiology of MSL SAT
MSL SAT may arise from a stem cell population either des-
tined to form BAT, or WAT that transdifferentiates to BAT;
in either case, UCP-1 levels help track BAT features. SAT
cells from subjects with MSL express UCP-1 suggesting its
origin as BAT[61, 70], but this is not substantiated in all cases.
Adrenergic receptors (AR) that respond to sympathetic input,
such as the three subtypes of β-AR, β1-, β2- and β3-, promote
lipolysis and energy expenditure. Cells isolated from the
MSL SVF did not increase UCP-1 in response to noradrena-
line even though MSL cells express all three β-AR. Resting
energy expenditure (REE) may be expected to be higher in
MSL with BAT; indeed REE when normalized to fat free mass
was mildly higher in MSL subjects than normal, suggestive
of energy uncoupling and heat generation, however, REE
in other subjects with MSL was within normal limits. In
MSL cell culture, catecholamines did not increase lipolysis,
expression of inducible nitric oxide synthase (iNOS) or PPARγ
coactivator-1α (PGC-1α), a coregulator of nuclear receptors
that control metabolic pathways in BAT[61, 73–75]. Two other
groups found a normally reactive adenylate cyclase system
and a normal number of a- and β-adrenergic receptors in
MSL SAT[76, 77]. Cytokine and adipokine levels in MSL are also
mixed[37, 61]. While the multilocularity of MSL SAT is sugges-
tive of BAT, more data in a larger number of subjects of well
characterized participants are needed to substantiate the cell
type of origin and functionality of pathways.
The increase in MSL fat is extensive and deforming, com-
pressing tissue structures and vessels. Early, MSL SAT is
watery but later becomes fibrotic and scars easily. Similarly
in obesity, excess fat physically impedes lymph collection
and flow, protein-rich lymphatic fluid collects in SAT, result-
ing in lymphedema and tissue hypoxia. SAT also grows
in the presence of lymphedema. Further accumulation of
fluid in the setting of decreased oxygen tension leads to fibro-
sis. Interestingly, ischemia activates the growth of adipose-
Figure 3. Whole body MSL and MSL-associated lipodystrophy. While MSL
is noted to spare the forearms (see text), the entire body can be clearly
affected. A, 60 year old woman with a history of alcohol dependence
with global MSL SAT; note prevalent SAT on the forearms (photo by Dr
Andy COREN). This type of MSL may be easily confused with global
obesity or lipedema stage III. B, 50 year old man with MSL Types I and II
with associated muscle and normal fat atrophy (also note the increased
back MSL SAT; arrows); this type of MSL may be confused with partial
Acta Pharmacologica Sinica
derived progenitor cells. Congestion of lymph nodes by
other means, such as lymphoma in the neck, induces fat
growth similar to MSL. Increased volumes of SAT in MSL,
like obesity, may therefore be sufficient to externally compress
vasculature and lymphatics inducing further growth of SAT as
seen in other localized fat collections. Impedance of lymph
flow into lymph collectors is a local effect and does not affect
flow in larger lymph trunks, therefore the role of lymphoscin-
tigraphy in MSL is questionable.
Conditions associated with MSL
Alcohol-induced liver disease is common in MSL. Hyper-
lipidemia, hyperuricemia, hypothyroidism, and diabetes
mellitus have been reported but are not consistent amongst
those affected[86, 87]. People with MSL I or II should be tested
for sleep apnea. Cancerous transformation of the SAT
is uncommon; development of myxoid liposarcoma was
reported in one case. Slowly progressive axonal sensory
and autonomic peripheral neuropathies have been reported
to occur after the development of MSL fat and impairment of
autonomic function has been suggested as a cause of sudden
death[86, 89]. The neuropathology is a distal axonal demyelina-
tion different from that associated with alcohol intake[58, 86, 90];
this impairment seems to be prevalently parasympathetic[48, 91].
In a ten year follow-up, ~10% of 31 patients died from sudden
death due to autonomic neuropathy. Surgical placement of
a cardiac pacemaker may be needed.
MSL treatment recommendations
1) Alcohol abstinence: Abstinence from alcohol may arrest
further progression of the MSL SAT but does not cause regres-
sion of the SAT deformities.
2) Lymphatic decongestive therapy (LDT): Includes manual
lymphatic drainage (MLD), wrapping of the limbs, compres-
sion garments, exercise such as pool therapy and other non-
impact exercise (so as to avoid lactic acid accumulation in tis-
sue due to poor lymph flow), dietary recommendations, and
skin care. Manual lymphatic drainage works well to reduce
MSL SAT before fibrosis.
3) Surgery: Surgical resection and liposuction provide the
only means of dramatically decreasing the MSL SAT[94–97]. In a
majority of cases of MSL Type II and III, resection or liposuc-
tion of the lipomatosis is considered cosmetic and insurance
companies are reluctant to cover this procedure. Unfor-
tunately, the fat usually penetrates and surrounds deeper
structures such as muscle and bone, making total excision of
the abnormal tissue difficult; the lipomatosis can, therefore,
recur after liposuction or excision[87, 99, 100]; in three of eleven
patients in one series.
Additional considerations for MSL treatment
4) β2-Adrenergic Agonist: After demonstrating an intact
lipolytic response of the MSL fat to catecholamines, an oral β2-
AR specific drug, salbutamol, 15 mg per day in divided doses,
reversed the rapid accumulation of the MSL fat and increased
REE in a man with MSL, but was effective only during active
5) Fibric acid: A man with MSL Type II with a past history
of hypertriglyceridemia was treated with fenofibrate 200mg
daily. The circumference of his abdomen decreased 119 cm
(46.9 in) to 108 cm (42.7 in) within a year. Fibric acids are
PPARα agonists. Activation of the PPARα receptor may sup-
press expression of proteins involved in the architecture of
BAT, thereby maintaining BAT in a quiescent state.
6) Growth hormone: Growth hormone (GH) treatment has
been suggested in the community of individuals with MSL as
a treatment option (personal communication) but GH levels
were normal in one subject with MSL during a glucose toler-
ance test and in three other subjects suggesting a normal
GH axis. Testing for GH deficiency should be undertaken and
replacement considered only for those deficient in this hor-
7) Lifestyle: Lifestyle improvements provide no resolution
of the MSL SAT.
8) Local SAT injections: Corticosteroid injections have been
suggested as treatment for lipomatosis such as MSL SAT
but there are a number of cases demonstrating the develop-
ment of lipomatosis after steroid use[107, 108]. Local injection
with thyroxine, enoxaparin, deoxycholate, and
phosphatidylcholine have also been proposed for treatment
of lipomas but the latter require multiple injections and use
of thyroxine injections in the presence of autonomic dysfunc-
tion would be dangerous. In addition, the extent of the SAT
in MSL does not allow for single site injections, limiting these
treatments to lipomas.
Lipedema (lipoedema; lipalgia; adiposis dolorosa; lipomatosis
dolorosa of the legs; lipohypertrophy dolorosa; painful column
Lipedema is generally unknown to medical providers, is eas-
ily confused as obesity, does not have a MESH term in the
National Library of Medicine, and does not have an Interna-
tional Classification of Diseases (ICD) code; it does have an
Online Mendelian Inheritance in Man code, and is recognized
by Orphanet (a European website providing information
about orphan drugs and rare diseases (Table 1). Drs Allen
and Hines Jr from the Mayo clinic labeled this condition as
lipedema in 1940. Outside the US, lipedema is known as
“lipoedema”, meaning edema of the fat. This disorder is likely
very common but underdiagnosed.
The diagnosis of lipedema is made clinically by history, visual
inspection and physical exam as extensive deposition of SAT
between the iliac crest and the malleoli and approximately
30% of the time, on the arm. When the fat is palpated, it
will be tender and feel like round peas in a plastic bag or
a “beanie baby”[111, 112]. Larger nodules, lumps, lipomas or
angiolipomas may also be found in the SAT. There are no
blood or urine biomarkers for lipedema and the gene(s) is
unknown. The skin and SAT is thicker in lipedema compared
Acta Pharmacologica Sinica
to healthy controls and muscle mass is not edematous as it is
in lymphedema. The skin is also less elastic and striae are
common in lipedema.
In 1951, Wold, Hines and Allen analyzed 119 cases and pro-
vided the diagnostic criteria for lipedema:
1) Almost exclusive occurrence in women developing by
the third decade of life. Prevalence within the population
remains grossly under diagnosed. According to an epide-
miologic study by Földi E and Földi M, lipedema affects
11% of the female population. At least seven cases have been
reported in men with testosterone or GH deficiency, or liver
disease[114, 115, 117].
2) Bilateral and symmetrical nature with minimal involve-
ment of the feet, resulting in an ‘‘inverse shouldering’’ or
‘‘bracelet” effect at the ankle
3) Minimal pitting edema (non-pitting edema is present)
4) Pain, tenderness, and easy bruising
5) Persistent enlargement despite elevation of the extremi-
ties or weight loss
6) Increased vascular fragility; easy bruising
Often women note that the lipedema appears or is exacer-
bated at the time of puberty, pregnancy or menopause sug-
gesting an estrogen component; that few men have this condi-
tion except those with hypogonadism or hyperestrogenemia
supports this hypothesis.
There are five types of lipedema
Type I: Pelvis, buttocks and hips (saddle bag phenomenon)
Type II: Buttocks to knees, with formation of folds of fat
around the inner side of the knee
Type III: Buttocks to ankles
Type IV: Arms
Type V: Lower leg
There may be a mixture of lipedema types in one person, for
example Type II and IV. Only the arms may be affected in 3%
of lipedema cases (Type IV). The importance of knowing
the different lipedema types is to improve recognition, and
identification of differences ie, all people with lipedema do not
look alike; treatment is similar amongst the types. In addition
to types of lipedema, the lipedema progresses through stages;
the progression varies greatly amongst those affected and
there is no data suggesting everyone need progress through
There are three stages of lipedema (Figure 4)[112, 120]
Stage 1: Normal skin surface with enlarged hypodermis
Stage 2: Uneven skin with indentations in the fat; larger
mounds of tissue grow as unencapsulated masses, lipomas
Stage 3: Large extrusions of tissue causing deformations
especially on the thighs and around the knees
Stage 4: Lipedema with lymphedema (lipolymphedema)
Progression to lipolymphedema can develop during stage
II-III. The description and representative pictures of Type III
MSL are that of lipedema stage II; no study has formerly
differentiated these two SAT disorders. Synonyms for lipe-
dema also include adiposis dolorosa, which is another name
for the RAD, Dercum’s disease (see below). However, accord-
ing to Cornely, the trunk, hands and feet are not involved
in lipedema “Thus, lipedema differs clearly from Dercum’s
disease”. As lipedema progresses to lipolymphedema, the
hands, feet, trunk and head develop excess SAT making this
statement incorrect. Because lymphatic dysfunction is a part
of Dercum’s disease and many early cases of Dercum’s disease
are visually and descriptively lipedema (see below), the two
SAT disorders are at a minimum, in the same spectrum. Lipe-
dema may also be confused with APL, however, in APL there
is a lack of SAT on the face and upper body while in lipedema,
SAT is normal or increased in these areas (Figure 1).
Inheritance of lipedema
Inheritance has been noted up to 60% of people with
lipedema[118, 123, 124] but is likely higher due to under diagno-
sis. In six families over three generations with lipedema, the
inheritance pattern was autosomal dominant with incomplete
Figure 4. The three stages of lipedema.
A, Stage I with little alteration of the skin
surface. B, In stage 2, the surface of the skin
takes on the appearance of a mattress with
lipomas in the fat. C, In stage III lipedema,
there are much larger fat extrusions.
Acta Pharmacologica Sinica
Histology of lipedema SAT
The gross description of the fat in lipedema is similar to that of
MSL with “free fluid fat” in biopsy specimens. Histologi-
cal exam is not unlike that found for cellulite with dilation
of subdermal blood capillaries, perivascular cells, fibrosis of
arterioles, fibrosis and dilation of venules, and hypertrophy
and hyperplasia of adipocytes[126, 127]. Histochemical studies
show adipocytes death and stem cell regeneration. There
are also increased numbers of blood vessels especially capillar-
ies and prominent venules. Large clusters of macrophages
are found around multiple fat cells (not isolated crown-like
structures), surrounding blood vessels and forming oil cysts
in lipedema SAT[116, 130]; macrophages may also be a prominent
component of cellulite. The histology of lipedema SAT can
also appear as normal.
Physiology of lipedema SAT
The elasticity of the skin and fascia is decreased in lipedema
which in Stage III may progress to abnormally clumped elas-
tic fibers or pseudoxanthoma. The skin loses its role as
an abutment for the skeletal muscle venous pump and the
increased compliance of the SAT results in an increase in
capillary compliance[116, 124]. The permeable capillaries release
excess protein-rich fluid into the interstitium along with
blood[42, 116, 134, 135]. The veno-arteriolar reflex in lipedema is also
absent so that under orthostatic conditions (standing), there
is limited vasoconstriction and increased net filtration driving
edema. Early on, lymphatic transport increases to accom-
modate the increased fluid flux from the capillaries[136, 137].
During this time, visualization of lymphatic vessels on a gross
level by lymphoscintigraphy is normal[138, 139]. As lipedema
progresses, microaneurysms appear in the lymphatics in the
skin[139, 140] which eventually leak[125, 136]. It is during this time
that hypertrophy and hyperplasia of fat cells accelerates
further altering the microlymphatic architecture and increas-
ing venous congestion. The resultant edema increases hydro-
static pressure in the tissue and pain[123, 141].
As an example of what happens in SAT when lymph leaks,
mutation of prospero homeoboxprotein 1, encoded by the
PROX1 gene, causes leakage from lymphatics and resultant
obesity in heterozygote mice. Lymph placed on adipocytes
in culture also induces robust growth; in essence, “lymph
makes you fat”. Although PROX1 mutations are not
known to be associated with lipedema, it is clear that fat grows
in response to lymph. Eventually, the microlymphatics may
become obliterated in lipedema leading to backflow and an
overall dynamic insufficiency of the lymphatic system. The
increased tissue pressure and lymphatic vessel leakage lead
to the development of lipolymphedema[136, 145, 146]. While lym-
phedema does not usually develop with cellulite in women,
the pathophysiology of cellulite development is similar to that
in lipedema, and LDT (see treatments below) improves the
cosmetic appearance of cellulite[147, 148]. Lipedema may there-
fore be an extreme form of cellulite.
Conditions associated with lipedema
Depression and anxiety are very common in people with lipe-
dema for many reasons including the lengthy time to diagno-
sis, repeated counseling on diet and exercise by the healthcare
community when neither is particularly effective and because
of the massive and sometimes rapid body metamorphosis over
a lifetime. In one clinic, women with lipedema were found to
be more depressed than patients with paralysis. Painful
SAT is a chronic problem in lipedema[111, 114]. The excess tis-
sue fluid weakens nearby structures leading to the develop-
ment of joint pains; with progression of lipedema, arthritis
develops. Capillary fragility, ecchymosis, hematomas and
venous varicosities are common. The Kaposi-Stemmer sign
is negative in lipedema (the skin cannot be pinched as a fold
by the fingers) until the development of lipolymphedema.
Idiopathic edema (IE) is similar to lipedema by description
and has been identified in women with lipedema[116, 134]. Other
changes in skin include dryness, fungal infections, cellulitis,
and slow wound healing. Free fatty acids may be different in
both blood and the lipedema SAT.
Lipedema treatments recommendations
1) Lymphatic Decongestive therapy (LDT) is the standard
of care for lipedema. Includes manual lymphatic drainage
(MLD), wrapping of the limbs, compression garments, move-
ment therapy, dietary recommendations, and skin care. LDT
has been shown to improve skin elasticity, restore the veno-
arteriolar reflex, increase pre-lymph drainage and lymph
transport in lymphatic vessels[116, 151], and reduce capillary
fragility in lipedema. Intermittent pneumatic compres-
sion may not improve limb size over MLD alone but may
be effective alone when MLD is not available. Compres-
sion is most effective when tissue edema is present as in its
absence, it has little effect. That compression was effective
in lipedema was noted by Hines in a woman with lipedema
whose fat and edema were absent under the area covered by
her “high-topped shoes”.
2) Exercise: Aqua lymphatic therapy (pool hydrotherapy)
significantly reduces limb volume in lymphedema. In addi-
tion to improving strength and bone mineral density, whole
body vibration (WBV) improves peripheral circula tion[159, 160]
and increases lymph flow, raising the threshold level for
edema formation in the legs. During WBV, the user simply
stands (or stretches/exercises) on a platform for 10-15 min.
making this a very accessible exercise modality.
3) Pain Control: Must be individually optimized; liposuction
improves pain (see below).
4) Psychological support: Many women with lipedema
are left on their own to find their diagnosis, convince their
healthcare providers about lipedema and then seek treatment,
all complicated by depression, anxiety and eating disorders;
counseling and support during treatment are necessary when
any of these are present. Counseling reduces anxiety by
50% in people with secondary lymphedema.
5) Surgery: Liposuction works effectively for lipedema to
Acta Pharmacologica Sinica
reduce SAT and pain[122, 163, 164]. In patients who have lipolym-
phedema, it may be prudent to undergo lymphoscintigra-
phy to confirm the absence of large lymph vessel damage
before pursuing liposuction. Bariatric surgery is ineffec-
tive in uncomplicated lipedema (without obesity or lym-
phedema)[165, 166] but effective in lipedema and lymphedema
associated with obesity as long as LDT is performed before
and after bariatric surgery.
Additional considerations for lipedema treatment
6) Beta-adrenergic agonist: Modeling treatment after capil-
lary leak syndrome, terbutaline sulfate, 5 mg five times daily,
and theophylline, 200 mg twice daily, were given to a woman
with lipedema (called lymphedema in the paper) and after 10
months a weight loss of 20 kg was noted. Cessation or lower-
ing the medication allowed weight regain.
7) Corticosteroids: Corticosteroids produce a fast reduction
in swelling and pain but increase the risk of infection, capil-
lary fragility and SAT growth. A series of corticosteroid joint
injections is usually well-tolerated without exacerbation of
8) Diuretics: Diuretics can quickly deplete lymphedema
fluid but concentrate protein in edematous tissue promoting
fibrosclerosis. Use of diuretics in lipedema before lym-
phedema may result in the development of pseudo Barrter’s
syndrome characterized by hypokalemic-hypochloremic alka-
losis, hyperactivity of the renin-angiotensin-aldosterone sys-
tem and elevation of atrial natriuretic peptide[116, 170].
9) Flavonoids: Daflon is a flavonoid that has been used to
treat lymphedema[171-173]; it may be expensive and is unlikely
available by prescription. Other flavonoids such as those for
venous disease have not been formerly tested in lipedema
participants. The International Society of Lymphology does
not endorse the use of flavonoids as a substitute for LDT.
10) Lifestyle: Obesity can occur along with lipedema espe-
cially in Stage III when the lipedema limits movement, but can
also occur when movement is limited by pain in earlier stages;
lifestyle improvements should always be considered but are
not the cause of lipedema. Lipedema SAT is unaffected by
caloric restriction alone.
11) Selenium: Sodium selenite (selenium) has proven effec-
tive for reduction of secondary lymphedema[169, 176–181]. The US
National Research Council has defined the individual maxi-
mum safe dietary intake for selenium as 600 μg daily and the
no adverse effect level as 800 μg daily.
12) Shock wave therapy: One report suggests that shock
wave therapy functions similarly to LDT in reducing oxidative
stress of the tissues and in smoothing the dermis and hypo-
dermis which may be useful as part of a treatment plan and
when lymphatics are still functioning.
Dercum’s disease (adiposis dolorosa; Morbus Dercums)
Dercum’s disease (DD) was recognized in 1892 as a clini-
cal entity called “adiposis dolorosa”, meaning painful fatty
deposits, when Dr Francis X DERCUM from the University
of Pennsylvania published on three cases. This senti-
nel publication was preceded by a report of a single case in
1888 and followed by the published autopsy of that case.
Numerous case studies, case series and descriptions of DD
have been published with such a wide variety of locations for
the fatty deposits, including misdiagnoses of obvious cases
of lipedema, familial multiple lipomatosis and MSL that,
unless one is an expert in SAT disorders, it would be difficult
to diagnose this often misunderstood syndrome. DD is cur-
rently considered to be a rare disorder (Table 1).
Diagnosis of DD is made by history and physical exam. Der-
cum’s disease occurs primarily in women with a ratio of
females to males of 5-7:1[186–188]; the average age of develop-
ment in one series was 35 years but it has been reported to
develop in children[188–191] and in adults up to age 80 years.
One in a 1,000 are affected in Sweden. Many cases of peri-
or post-menopausal women with DD have been reported sug-
gesting a hormonal component to the development of DD.
In addition to painful SAT, there are many other signs and
symptoms associated with DD so a lengthy review of systems
is helpful (Table 2).
There are three types of DD[187, 193]:
Type I, juxta-articular (around the joint): Painful folds or
nodular fat on the inside of the knees and/or on the hips; in
rare cases only evident in the upper-arm fat (similar to Type
Type II, diffuse, generalized type: Widespread pain from
fatty tissue found anywhere from head to the soles of the feet.
Type III, nodular type: Intense pain in and around multiple
“lipomas”, sometimes in the absence of obesity.
Interestingly, the painful lumps of fat first noticed around
joints in DD Type 1 occur in locations of lymph nodes, for
example around the knee (popliteal nodes), the elbow (cubit
nodes), hips and thighs (inguinal nodes), upper arm (axillary
nodes) and supraclavicular. As Dr Kling reported in 112 cases
of Type I DD, “Juxta-articular adiposis dolorosa is regarded as
the initial and intermediate stage of generalized adiposis dolo-
rosa”. Dercum’s disease Type I is therefore, the first stage
of DD, and Type II a stage with more widespread dysfunction.
Type I DD around the knees is visually consistent with Type
IV and Type II lipedema Stages 2–3.
Type III DD is likely a variant of familial multiple lipoma-
tosis (FML) in which men present mainly with lipomas and/
or angiolipomas predominating on the lower and upper
arms, the lower trunk and thighs and women present with
lipomas, angiolipomas and obesity[188, 195]. Angiolipomas can
be found in up to 30% of people with DD[188, 196]. The lipomas
are generally not painful in FML except if they are growing
or traumatized frequently, however, they are painful in DD
Type 3. In a DD family, family members may have lipomas
without pain. Even if a person with FML has non-painful
lipomas, at some point in time a lipoma can become painful,
followed by generalized pain in all lipomas. Pack and Ariel
described this as lipoma dolorosa, distinct from DD. It is
Acta Pharmacologica Sinica
unclear why the authors make this distinction as others ascribe
the same pathological process to both FML and DD Type III,
with pain in the latter due to “local conditions”. The “local
conditions” may be increased tissue tension from fluid accu-
mulation. In two cases of DD Type III, pain was relieved after
local hemorrhage. The underlying pathophysiology of DD
needs to be elucidated to further differentiate or group the
three types of DD.
DD inheritance: Thought to be autosomal domin -ant[188, 195,
199, 200]. In two families, females were more affected than males
suggesting a sex-specific influence on the expression of the DD
Histology of DD
Some of the unilocular adipocytes are extremely large in DD
SAT compared to weight matched controls. Dr Dercum
and others found an infiltration of nerves (neuritis)[185, 201] but
this has not been substantiated. Increased connective tissue
around nerves, blood vessels and as thickened septae has been
noted[185, 202, 203]. Perivascular cells, giant cells, and granu-
lomas suggestive of a foreign body reaction are apparent in
some areas. The histology of DD SAT can also appear nor-
Physiology of DD
The physiology of DD is unknown and many etiologies have
been advanced. These include thyroid dysfunction, pitu-
itary dysfunction, polyglandular disease, infection, neuritis,
alcohol, trauma, a defect in the synthesis of long chain fatty
acids, lower resting energy expenditure, and altered
responses to norepinephrine and insulin.210 Ballet may have
been closest to the actual etiology when he stated that it is a
“chronic intoxication of endogenous origin”. The evidence
currently points to an underlying vascular and lymphatic
dysfunction in DD Types I/ II similar to lipedema (Birgher
Fagher, personal communication) for the following reasons:
1) Vascular dysfunction as hematemesis[212, 213], epis-
taxis[213, 214], hemaochezia, heavy menses[215, 216], varicose
veins, and altered vasoconstrictor responses is common
in both lipedema and DD. Perivascular infiltration of immune
cells have been found in DD tissue suggesting damage to
or repair of blood vessels, and brain vasculitis in DD has been
2) LDT has been reported to be beneficial in DD220 as in lipe-
3) Multiple lipomas can develop in lipedema as in DD.
4) Fibrosis secondary to lymphedema is common in lipe-
dema and DD.
5) In the presence of lymphatic and vascular dysfunction in
lipedema, the fat is painful, similar to DD.
6) In the German literature, lipedema is known as adiposis
dolorosa, another name for DD.
7) Original descriptions of DD match descriptions of lipe-
dema. For example, Spiller described a woman with pain-
ful fat as follows: “The obesity was marked over the thighs,
calves, abdomen, nates (buttocks), and back. It was also very
great in the arms, less marked in the forearms, and absent in
the feet and hands”. Dr Collins noted that “The fatty accu-
mulations have not been noticed in the hands, face or feet,
and frequently the contrast between the feet which preserve
their normal outline and contour and the legs, when the latter
are involved, is most striking”. These cases are similar to
lipedema in terms of the pattern of painful fat (less likely early
on in the hands, feet, face, and forearms) and the latter case
describes well the distinct “bracelet” of fat seen at the base of
the leg above the foot that is classic in lipedema. The pub-
lished photographs of the columnar legs with the cuff of fat
above the foot, or the mass of tender fat inferomedial to the
knee, and the enlarged upper arms in DD are consistent with
lipedema[112, 183, 184, 224, 225].
8) The nodular “beans in a bag” feel of the fat in lipedema is
the same as in DD Types 1 and 2[188, 226].
9) Dr Dercum described DD as a disorder of the “haemo-
lymph system” though the importance of these structures
in humans is unclear. Hemolymph nodes are structures
resembling a lymph node, but which can have blood in the
sinuses; erythrocytes enter the hemolymph nodes through
afferent lymphatics. There are few reports on the function
of hemolymph glands in humans.
10) Dr Mills reported “In one case studied carefully with
Dr Dercum, there was a general disease of the lymphatic sys-
The data suggest that the vascular and lymph system are
dysfunctional in both lipedema and DD, that pre-lymph
remains in the tissue longer, inducing fat growth and the
characteristic beans in a bag feel to the fat. In both lipedema
and DD there is a hereditary component[195, 199]. Also in both
cases, estrogen and/or progesterone likely play a role result-
ing in the predominance of women with lipedema and/or
DD; lipedema is known to occur with the onset puberty and
pregnancy, and DD with menopause, both times of chang-
ing hormone levels. In DD, a more widespread insult to
the vascular and lymphatic system may occur compared to
lipedema. Many of the early reported cases of DD had syphi-
lis[213, 216, 230], well known to affect the lymph nodes, consumed
alcohol[214, 231] which acutely increases mesenteric lymphatic
pumping but decreases lymphatic myogenic tone, or had
antecedent trauma which may have affected lymphatic func-
tion[207, 213, 233]. Many patients with DD Type I or II noticed their
first painful area of fat after a viral flu, severe pneumonia or
trauma[188, 213, 234]. Data are needed on lymphatic function in
DD to confirm these hypotheses.
Conditions associated with DD
In addition to the two cardinal symptoms of fatty deposits
and pain proposed by Dercum, Vitaut added the third car-
dinal symptom of DD, asthenia (abnormal physical weakness
or lack of energy). Accessory symptoms in DD are found
in the psychiatric, motor, sensory and sympathetic nervous
systems as well as the pulmonary, endocrine, gastrointesti-
nal and rheumatological systems[187, 188, 235] (Table 2).
Thyroid dysfunction has been suggested as one etiology of
Acta Pharmacologica Sinica
DD. While a few cases of DD benefited from thyroid treat-
ment[216, 236] many cases of DD failed to improve[192, 215, 230, 237, 238]
and DD generally continues to progress during adequate
thyroid replacement. Others have suggested multiple
endocrine dysfunction as a cause for DD (reviewed) but
ACTH and pituitary extract did not improve signs and symp-
toms associated with DD[192, 239] and hormone testing was nor-
mal in other cases[210, 240]. If hypercholesterolemia is present,
severe and generalized vascular disease may be found.
DD treatment recommendations
1) Exercise: Similar to lipedema. Supporting the use of WBV
as exercise in DD, WBV slowed the acquisition of fat in female
rats and improved pain and fatigue in women with fibro-
2) LDT: LDT220 and “massage” are known to be beneficial
for DD Types I and II; recommendations are similar to lipe-
dema (see above).
3) Pain control: Must be individually optimized; only pub-
lished or important anecdotal reports are included here:
(a) Chemotherapy: A patient with DD had improved pain
and growth of DD SAT slowed on methotrexate combined
with infliximab. One case had resolution of her lipomas
and pain with paclitaxel and carboplatin (unpublished); once
the paclitaxel was discontinued because of neuropathy, the
pain and lumps returned.
(b) Cyclic Variations in Adaptive Conditioning (CVAC™):
A novel therapy that reduces tissue fluid by variable pattern-
ing of different atmospheric pressures around a person sitting
in an altitude simulator. Peri-corporal pressure patterns vary
from sea level to four sequential altitude levels: 3200 m (10.5K
ft), 4419 m (14.5K ft), 5638 m (18.5K ft), and 6858 m (22.5K ft).
This ‘body conditioning’ reduced fluid and pain in 10 DD par-
ticipants and improved VO2max in healthy men.
(c) Lidocaine: Intravenous (IV) lidocaine has been used
with some success to treat the intractable pain associated with
DD[217, 247–253]. Many individuals with DD obtain good local
pain relief using lidocaine patches, cream, gel or EMLA[248, 254].
(d) Mexilitene: Mexilitene (an antiarrhythmic drug) has
been used for the effective treatment of pain in DD.
(e) Pregabalin: LDT combined with pregabalin (an anti-
convulsant drug used for neuropathic pain) has been used to
treat the pain associated with DD.
4) Psychological support: See lipedema (above).
5) Surgery: Liposuction is one of the accepted methods of
treatment for DD[196, 255–257] resulting in decreased pain[258, 259].
When asked specifically about liposuction in a series of 110
patients, 83 respondents (75.5%) reported having had lipo-
suction; of these, 50.6% reported that the painful fat depots
grew back. Surgical resection and liposuction should be
preceded by LDT and compression to support all vasculature
and decrease the risk of seroma and hematoma formation. DD
may be one reason why RYGBP without LDT failed to result
in weight loss in a published case.
6) Aminoacetic acid (glycine) and prostigmine: In three
women with DD, a diet consisting of 70 grams protein, 70
grams of fat and 100 grams carbohydrate or 1500 calories/day
(specifics unavailable), 10 grams glycine and 45 mg prostig-
mine daily improved weight loss and energy. If glycine
binding in the central nervous system is antagonized, feeding
in rats increased; glycine may therefore be an appetite sup-
pressant while prostigmine improves asthenia.
7) Corticosteroids (oral): Cortisone treatment has been
shown to help with pain but with none of the other features of
DD; cortisone treatment can also induce DD. A series of
corticosteroid joint injections is usually well-tolerated without
exacerbation of symptoms and signs in DD.
Table 2. Cardinal and accessory signs and symptoms of Dercum’s disease with checkbox.
Pain in fat deposits for at least 3 months
Pain exacerbated by stress, strenuous exercise, trauma, changes in weather, or other; pain can be
spontaneous or on palpation; may wax and wane or move around
Exacerbated by activities of daily living or exercise
Joint pain and/or stiffness
Shortness of breath
Visible vascularity near lipomas; telangiectasias; multiple cherry angiomas, multiple petechiae; easy
Increased in areas of fat deposits
Especially on awakening or the day after physical activity
In the presence of normal oxygen saturation or as part of the need for oxygen supplementation
Varies from palpitations to supraventricular tachycardia requiring beta-blockade
Acta Pharmacologica Sinica
8) Hormonal testing: Testing for thyroid function and
assessing a complete panel of pituitary hormones at least once
after diagnosis of DD and when symptoms change is prudent
so as not to miss accompanying hormonal dysfunction, which
should be treated with usual methods. Adipose tissue is a
very hormonally responsive tissue, so estrogen, progester-
one and testosterone levels should be monitored regularly on
any replacement regimen so as to regulate high and low levels
and avoid wide fluctuations.
9) Lifestyle: While obesity is prominent in DD, the DD SAT
is resistant to loss with lifestyle changes[261, 266] while normal
SAT as part of obesity can be lost.
10) Oxygen therapy: Many people with DD feel short of
breath. This can progress on to the need for continuous
oxygen therapy. It is unclear why the shortness of breath
occurs but it is likely a combination of increased interstitial
fluid moving cells away from their oxygen source and a weak-
ened diaphragm. Pulmonary function testing should be per-
formed on everyone with DD that has shortness of breath even
if it serves simply as a baseline for future changes or symp-
toms. Similar to MSL, if a patient has increased thickened fat
around the chest or neuropathy, DD patients with shortness of
breath and/or edema should be evaluated for thoracic outlet
syndrome, sleep apnea and/or autonomic dysfunction.
Co-morbidities associated with obesity in DD are treated as
Obesity is very common and in the limited time allotted to
patient care, it may be easy to misdiagnose a patient with a lip-
odystrophy or a RAD disorder as having simple obesity, and
prescribe lifestyle changes only. The widespread increase in
abnormal SAT in MSL, DD or lipedema Type II or III can eas-
ily masquerade as global obesity (Table 3). The loss of normal
fat and muscle in MSL or the disproportion of fat in lipedema
can also be confused with lipodystrophy; lipedema Type I is
usually overlooked. Lifestyle changes and bariatric surgery
work effectively for the obesity component of FPLD and RADs
but not for the abnormal SAT tissue in RADs. The RAD SAT
likely results from the growth of a brown stem cell population
that secondarily compresses lymphatics and vessels (in MSL)
or a primarily vascular and lymphatic dysfunction with sec-
ondary growth of SAT (in lipedema and DD), neither of which
respond well to caloric limitation. Academic testing of various
dietary regimens, mechanical treatments, surgery, medica-
tions, and supplements is needed for RADs. Understanding
the genomics of the RADs is also important to help differenti-
ate lipedema, MSL and DD especially in women where the
three disorders can look so much alike, and to assess for RADs
in obesity. Improved recognition of RADs may also prove that
lipedema and DD are not RADs at all but common disorders
and that understanding the underlying pathophysiology of
RADs may improve our understanding of refractory obesity.
Lymphatic drainage methods used for RADs should be con-
sidered in resistant obesity cases or before bariatric surgery,
low to very low calorie diets or other methods that induce
rapid weight loss requiring optimal lymphatic function.
This study received research support from the UCSD NIDDK
Diabetes and Endocrinology Research Center Grant P30
DK063491 and the UCSD General Clinical Research Center by
Public Health Grant 5M01RR000827. This paper is dedicated
to people with RADs and to Birgher Fagher, MD, who died in
April of 2011.
Conflicts of interest
This study was approved by the University of California, San
Table 3. Comparison of RAD characteristics.
Abnormal SAT location
Time of SAT change
Common in males
Obesity; HIV lipodystrophy
Autosomal?dominant?or?recessive? Autosomal?dominant;?sex-specific?influence? Autosomal?dominant;?incomplete?penetrance
tRNALys mutations uncommon None
Child to adult
Large nodular fat masses
Puberty; by third decade
* Can be global especially in women; APL=acquired partial lipodystrophy; FML=familial multiple lipomatosis; RAD=rare adipose disorder;
SAT=subcutaneous adipose tissue
Acta Pharmacologica Sinica
Diego Human Research Protection Program and the Research
and Development Committee at the Veterans Affairs San
Diego Healthcare System. All subjects described herein com-
pleted an informed consent process prior to enrollment.
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