Lipodystrophy is a group of rare diseases characterised by the generalised or partial absence of adipose tissue. The spectrum of its appearance can range widely but is often accompanied by metabolic changes like insulin resistance; this promotes the occurrence of hard to treat diabetes, dyslipidaemia and cardiovascular complications. Due to its rarity, the diagnosis of lipodystrophy may be missed as most clinicians are not familiar with its diagnosis and management.

How can I detect lipodystrophy?

Generalised and partial lipodystrophy may be hard to detect. If you suspect your patient to have lipodystrophy, the following questionnaire, based on the publication by Araujo-Villar D et al.1 can help you to confirm whether your patient has the disease.

Is adipose tissue recovery possible?



Your patient does not have lipodystrophy

Do aging traits exist?



Your patient may have progeria syndrome

Is the fat loss generalised, partial or localised?




Your patient may have localised lipodystrophy due to:
- lipodystrophy semicircularis
- centrifugal lipodystrophy
- panniculitis-associated lipodystrophy
- drug injections

Familial consanguinity or other relatives affected?



Your patient may have congenital generalised lipodystrophy known as Berardinelli-Seip Syndrome

Did signs first occur before 1 year of age?



Your patient may have congenital generalised lipodystrophy known as Berardinelli-Seip Syndrome

Did fat loss first occur in childhood?



Are any inflammatory signs obvious?



Your patient may have autoinflammatory lipodystrophy

Is fat accumulation present around the face and neck or around hips and legs?



Your patient may have acquired partial lipodystrophy known as Barraquer-Simons Syndrome

Did the patient receive a bone transplant in childhood?



Your patient may have a bone marrow transplant associated lipodystrophy

Your patient may have familial partial lipodystrophy known as Dunnigan or Köbberling type

Has the patient had an autoimmune disorder or paniculitis?



Your patient may have acquired generalised lipodystrophy known as Lawrence Syndrome

Your patient may have acquired generalised lipodystrophy known as Lawrence Syndrome


Your patient may have congenital generalised lipodystrophy known as Berardinelli-Seip Syndrome

Genetic testing

In congenital and familial forms of lipodystrophy, genetic testing can be useful in classifying the type of lipodystrophy.  However, genetic defects have yet to be identified for some hereditary forms such as FPLD1. Once a genetic cause has been identified, genetic councelling and family screening may be appropriate.

What are the different forms of lipodystrophy?

Lipodystrophies are potentially life threatening diseases, heterogeneous in appearance, very rare, and characterised by a partial or complete loss of subcutaneous fatty tissue. However, there are external signs of illness and ones that are only displayed on examination. Symptoms manifest differently in each patient and not all of these symptoms have to occur in all patients. The disease is subdivided according to four primary categories: CGL, AGL, FPLD and APL.

Lipodystrophy is heterogenous in appearance – but it is always linked to a lack of subcutaneous adipose tissue.

Generalised and partial lipodystrophy can be considered a visual diagnosis, therefore the patient must be examined unclothed. However, in addition to the unusual appearance of a lipodystrophy patient, there are also other conspicuous clinical symptoms. These can essentially be traced back to leptin deficiency and ectopic fat storage. Leptin deficiency usually causes high triglyceride levels with the risk of pancreatitis and insulin resistance that may lead to hard to treat diabetes. Patients may have hormone imbalances, insatiable hunger and hyperphagia, and liver disease due to fat accumulation. Although lipodystrophy cannot be cured there are some treatments available to help manage the metabolic complications of the disease.

An overview of the clinical features for the different lipodystrophy subtypes can be found in the table below:

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Overview of clinical findings for GL and PL


Congenital GL

Acquired GL

Familial PL

Acquired PL

Time of manifestation

Infancy to early childhood

Childhood to adult age

Childhood to adult age

Childhood to adult age

Fat loss locations

Face and neck


Upper extremities

Lower extremities


Fat accumulation/sparing

Face and neck

Hips and buttocks

Lower extremities


Other signs

Accelerated linear growth

Acromegaloid features

Umbilical prominence




Acanthosis nigricans




Hyperandrogenism in women

Essential finding

Supportive finding

Clinical characteristics of lipodystrophy

Both forms, generalised and partial lipodystrophy, can be familial or acquired; prevalence is less than 1 per million (generalised forms) and less than 3 per million (partial forms). There are also further subtypes with partially defined genetic characteristics and different manifestations. The cause of the acquired forms has not yet been clarified sufficiently. Autoimmune and/or infectious causes are being discussed.

Generalised Lipodystrophy

Congenital generalised lipodystrophy (CGL) is considered to be an autosomal recessive disorder that is characterised by early onset at birth or infancy. Serum leptin levels are typically very low in patients with CGL. However, serum leptin levels alone are not a sufficient parameter for diagnosis as they vary according to the time of day and depend on sex, age, BMI and metabolic state. So far, no accepted normal value ranges have been established. The acquired subtype of generalised lipodystrophy (AGL) is defined by progressive subcutaneous adipose tissue loss affecting the whole body including palms and soles. It usually appears before adolescence but can also develop at any time in life.

Partial Lipodystrophy

With familial partial lipodystrophy (FPLD) in particular, subcutaneous loss of fat may not be immediately obvious if the patient is examined while clothed. Attention should be paid to any loss of subcutaneous adipose tissue on the arms or legs. In contrast, there can be fat accumulation in the area of the face and neck (buffalo’s or bull’s neck), particularly in women which can present as a Cushingoid appearance. The ectopic, intra-abdominal fat deposits and corresponding increase in abdominal girth can lead to an obese appearance.

In the acquired form of partial lipodystrophy (APL), loss of adipose tissue is gradual, starting at the head and progressing down to the upper abdomen. There can, however, be fat accumulation in the areas of the buttocks, hips and lower extremities. The typical “saddlebags” appearance develops.


For detailed information about the different subtypes please click on the pictures below. Please be aware that the patient being shown are only example of cases Appearance might differ considerably according to the subtype.

(Berardinelli-Seip Syndrome)

(Lawrence Syndrome)

(Dunnigan or Köbberling type)

(Barraquer-Simons Syndrome)

Mean age of onset

0.3 years (range 0.0-12.0 years)

5 years (range 0.0-15.0 years)

9.9 years (range 0.0-16.0 years)

8.2 years (range 0.5-16.0 years)

Gender distribution
(male : female)





Typical appearance

  • Muscular appearance with prominent veins and umbilical prominence
  • Enlarged liver
  • Hyperphagia, accelerated linear growth, advanced bone age or acromegaloid features
  • Precocious puberty and rarely, premature pubarche and menarche
  • More common in ethnic groups with instances of parental consanguinity
  • Progression of adipose tissue loss takes weeks or years
  • Hyperphagia
  • Hyperkeratosis, and generalised or localised pigmentation
  • Enlarged liver
  • Appearance may be Cushingoid or resembling obesity
  • Fat accumulation around the neck in some subtypes
  • Hyperphagia
  • Adipose tissue loss occurs in cephalocaudal fashion
  • Progression of adipose tissue loss may take months or years
  • Fat accumulation around the hips or legs

Signs and symptoms

  • Comorbidities are common and severe
  • Hepato- and splenomegaly
  • Diabetes mellitus and acanthosis nigricans
  • Irregular menstrual periods, hirsutism, hyperandrogenism, polycystic ovaries, and/or infertility in females
  • Presence of autoimmune diseases or panniculitis
  • Hepato- and splenomegaly
  • Diabetes mellitus
  • Hirsutism, hypogonadism and acanthosis nigricans
  • Metabolic abnormalities develop during adulthood
  • Diabetes and acanthosis nigricans
  • Hirsutism and hyperandrogenism in females
  • Hepatomegaly
  • Metabolic complications are less common
  • Main cause of morbidity is renal disease due to autoimmunity which may lead to kidney failure

Subtypes seen
(Causes and effects)

  • CGL1: AGPAT2 mutations- Patients lack metabolically active fat
  • CGL2: BSCL2 mutations - Most severe form, patients lack mechanical and metabolically active fat; they may also suffer from mental retardation
  • CGL3: Caveolin 1 (CAV1) mutations - Associated with short stature and vitamin D resistance, only one patient known
  • CGL4: Polymerase I and transcript release factor (PTRF) mutations - Extreme lack of body fat, associated with pyloric stenosis
  • Causes of lipodystrophy not fully known
  • FPLD1: Unknown cause - Loss of gluteal and limb fat, but leptin levels often unaffected
  • FPLD2: Lamin A/C mutations – Fat accumulation around neck and reduced leptin levels
  • FPLD3: Peroxisome proliferator activated receptor gamma (PPARG) mutations
  • FPLD4: Perilipin 1 (PLIN1) mutations
  • FPLD5: Cell-death-inducing DNA, fragmentation factor a - like effector c (CIDEC) mutations
  • FPLD6: Adrenoceptor alpha 2A (ADRA2A) mutations -  Fat accumulation around neck
  • FPLD7: Hormone-sensitive lipase (LIPE) mutations
  • Causes of lipodystrophy not fully known (autoimmune or genetic)

Differential diagnosis

The path to diagnosis can be difficult and long. According to the subtype, onset of lipodystrophy symptoms may occur between infancy and adolescence. Health complications associated with the disease can vary greatly. In particular, patients suffering from partial lipodystrophy do not necessarily display any symptoms until puberty. Special attention should be paid to FPLD as this might be confused with truncal obesity, Cushing’s syndrome and multiple symmetric lipomatosis. Hence, lipodystrophy can be often misdiagnosed and differential diagnosis should include conditions aligned with severe weight loss such as:
- anorexia nervosa
- uncontrolled diabetes mellitus
- thyreotoxicosis
- adrenocortical insufficiency
- cancer cachexia
- chronic infections

Both, severe metabolic syndrome and  lipodystrophy exhibit extreme hypertriglyceridaemia making a differential diagnosis difficult.

1 Araujo-Villar D et al.(2019): Diagnosis and treatment of lipodystrophy: a step‑by‑step approach. J Clin Invest 42:61–73