Lipodystrophy – an Insight into a Rare Condition with Severe Metabolic Consequences
Katrina Mountfort, Senior Medical Writer, Touch Medical Media, UK
Matthew Goodwin, Group Director and Advisory Editor, Touch Medical Media, UK
-Insights into lipodystrophies, presented at the ECE congress, Barcelona, Spain, Monday 21 May 2018

Lipodystrophy syndromes are very rare disorders, with prevalence estimates ranging from 1.3–4.7 cases/million,1 that are characterised by loss of subcutaneous adipose tissue. They are highly variable in their presentation and are categorised based on aetiology (genetic or acquired) and distribution of lost adipose tissue: affecting the entire body (generalised) or only certain regions (partial). Depending upon the severity and extent of body fat loss, patients may also be predisposed to metabolic abnormalities including insulin resistance and dyslipidaemia, pancreatitis, non-alcoholic fatty liver disease (NAFLD) and, in females, hyperandrogenism, polycystic ovarian syndrome and subfertility.2 Due to the rarity and heterogeneity of these syndromes, many clinicians are unfamiliar with their diagnosis and management. As a result, lipodystrophy is frequently unrecognised or misdiagnosed, a growing concern since it is a progressive condition and its complications are potentially life threatening. The 20th European Congress of Endocrinology (ECE), which was held on the 19–22 May 2018 in Barcelona, Spain, featured a symposium, entitled, ‘All you need to know about lipodystrophy.’ In this article, we provide an overview of lipodystrophy, its diagnosis and management.

The two main types of genetic lipodystrophies are congenital generalised lipodystrophy (Berardinelli-Seip syndrome), an autosomal recessive syndrome, and familial partial lipodystrophy, mostly an autosomal dominant syndrome.3 Berardinelli-Seip syndrome is characterised by an almost complete absence of fat from birth or infancy. Patients may also have acanthosis nigricans, hepatomegaly and an umbilical hernia, as well as a voracious appetite. They often develop diabetes and/or hypertriglyceridemia in childhood or adolescence.3

Familial partial lipodystrophy may be caused by a number of mutations and is classified into one of five subtypes (types 1–5) based on the genetic cause.4 It typically presents around puberty and is characterised by loss of fat affecting the limbs, buttocks, and hips, as well as the accumulation of excess fat in certain regions.2,4 Since puberty is a time of rapid growth and development, its diagnosis may be delayed for many years, especially in men. The pattern of fat loss also varies according to the genetic diagnosis.4,5 Metabolic abnormalities are often seen in adult patients, including increased risk of coronary heart disease and early cardiomyopathy,6 yet therapeutic options for them are currently limited as patients often do not qualify for therapies such as glucagon-like peptide 1 (GLP­1) agonists and weight loss interventions, as their body mass index typically falls into the overweight or obese (25–35 kg/m2) category rather than the morbidly obese (>40 kg/m2) range.

Acquired forms of lipodystrophy are characterised by a progressive loss of adipose tissue, typically in childhood or adolescence, but onset may occur in adulthood. They may affect almost the entire body (generalised, e.g. Lawrence syndrome) or only certain body regions (partial, e.g. Barraquer-Simons syndrome).7 They are also associated with metabolic abnormalities including insulin resistance, type 2 diabetes, hypertriglyceridemia, reduced leptin levels, hepatomegaly and steatosis. The pathogenic mechanism underlying acquired lipodystrophy is not known. Many patients have an underlying cause such as associated autoimmune diseases, dermatomyositis, autoimmune hepatitis and mesangiocapillary glomerulonephritis, or a malignancy such as lymphoma.2 Other potential causative factors have been proposed, including adipocyte AKT, reduced levels of complement and the presence of a ‘C3 nephritic factor’ auto-antibody.8,9 Acquired lipodystrophy may occur in HIV patients as a result of long-term highly active retroviral therapy treatment. These drugs affect adipocytes by a number of mechanisms including mitochondrial dysfuntion,10 increased local inflammation, and impaired hormonal production or molecular signalling.11 Other causes of acquired lipodystrophy include bone marrow transplant occurring during childhood.12 In addition, cytotoxic treatments such as total body irradiation may affect the normal development of fat mass.

Lipodystrophy should be suspected in patients with regional or generalised lack of adipose tissue. Diagnosis is based on history, physical examination, body composition and metabolic status. Anthropometry, dual energy x-ray absorptiometry, and whole-body MRI may be used to establish a diagnosis. Confirmatory genetic testing is helpful in patients with suspected familial lipodystrophy. Serum complement levels and the presence of autoantibodies may support a diagnosis of acquired lipodystrophy syndrome.13 It can be particularly difficult to differentiate lipodystrophy from uncontrolled diabetes as both may have concurrent hypertriglyceridemia. The main distinguishing factor is that restoring glycaemic control in patients with diabetes leads to a regain of body fat. Following a diagnosis of lipodystrophy, regular screening should be performed for diabetes, dyslipidaemia, NAFLD, and cardiovascular and reproductive dysfunction.

There are no curative therapies for lipodystrophy so its management includes lifestyle changes involving diet and exercise.13 Avoiding excess dietary calorie intake, despite the often lean appearance of the patient, is essential to avoid short- and long-term complications, while allowing normal growth in children. Other treatment recommendations relate to specific comorbidities such as diabetes, dyslipidaemia, hypertension and liver disease. Cosmetic procedures such as autologous fat transfer may be prescribed for distressing changes in physical appearance.13

A key clinical characteristic of lipodystrophy is low or undetectable levels of the adipose-derived cytokine leptin. Leptin replacement therapy has therefore been investigated for the treatment of metabolic dysfunction, mainly in generalised lipodystrophy.14 Metreleptin (recombinant human methionyl leptin, MyaleptTM, Aegerion Pharmaceuticals, Cambridge, MA, US), has proven remarkably effective in controlling metabolic parameters that have not responded to conventional therapy,15 and is the only drug approved specifically for lipodystrophy. It is approved by the US Food and Drug Administration as an adjunct to diet for the treatment of metabolic complications in patients with generalised lipodystrophy, and in Japan for both generalised and partial lipodystrophy.16 Due to the potential of adverse events, including the development of neutralising antibodies and increased risk of lymphoma, metreleptin is only available through a restricted program called the Myalept Risk Evaluation and Mitigation Strategy Program. Physicians must be enrolled and certified in the program in order to prescribe Myalept. In Europe, it is available via a compassionate use programme, and a marketing authorisation application has been submitted to the European Medicines Agency. The evidence base for the use of metreleptin in partial lipodystrophy is incomplete; more studies are needed.13,17

In summary, lipodystrophy syndromes may be hard to recognise and are associated with underlying metabolic disturbances, which can be difficult to manage with traditional therapies. Following the emergence of metreleptin as an effective treatment for generalised, and potentially for partial lipodystrophy syndromes, it is important to raise awareness of this rare but devastating condition.


1. Chiquette E, Oral EA, Garg A, et al. Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges. Diabetes Metab Syndr Obes. 2017;10:375–83.
2. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350:1220–34.
3. Agarwal AK, Simha V, Oral EA, et al. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab. 2003;88:4840–7.
4. Guillin-Amarelle C, Sanchez-Iglesias S, Castro-Pais A, et al. Type 1 familial partial lipodystrophy: understanding the Kobberling syndrome. Endocrine. 2016;54:411–21.
5. Strickland LR, Guo F, Lok K, et al. Type 2 diabetes with partial lipodystrophy of the limbs: a new lipodystrophy phenotype. Diabetes Care. 2013;36:2247–53.
6. Hegele RA. Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. Mol Genet Metab. 2000;71:539–44.
7. Misra A, Garg A. Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Medicine (Baltimore). 2003;82:129–46.
8. Yavuz S, Acarturk TO. Acquired partial lipodystrophy with C3 hypocomplementemia and antiphospholipid and anticardiolipin antibodies. Pediatr Dermatol. 2010;27:504–8.
9. Shearin AL, Monks BR, Seale P, et al. Lack of AKT in adipocytes causes severe lipodystrophy. Mol Metab. 2016;5:472–9.
10. Perez-Matute P, Perez-Martinez L, Blanco JR, et al. Role of mitochondria in HIV infection and associated metabolic disorders: focus on nonalcoholic fatty liver disease and lipodystrophy syndrome. Oxid Med Cell Longev. 2013;2013:493413.
11. Caron M, Vigouroux C, Bastard JP, et al. Antiretroviral-related adipocyte dysfunction and lipodystrophy in HIV-infected patients: Alteration of the PPARgamma-dependent pathways. PPAR Res. 2009;2009:507141.
12. Ceccarini G, Ferrari F, Santini F. Acquired partial lipodystrophy after bone marrow transplant during childhood: a novel syndrome to be added to the disease classification list. J Endocrinol Invest. 2017;40:1273–4.
13. Brown RJ, Araujo-Vilar D, Cheung PT, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016;101:4500–11.
14. Ebihara K, Kusakabe T, Hirata M, et al. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2007;92:532­–41.
15. Oral EA, Simha V, Ruiz E, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002;346:570–8.
16. US FDA approves orphan drug MYALEPT™ (metreleptin for injection). Available at: (accessed 21 May 2018).
17. Rodriguez AJ, Mastronardi CA, Paz-Filho GJ. New advances in the treatment of generalized lipodystrophy: role of metreleptin. Ther Clin Risk Manag. 2015;11:1391–400.