eMedicine Specialties > Endocrinology > Metabolic Disorders

Lipodystrophy, Acquired Partial

Author: George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
Coauthor(s): Robert A Gabbay, MD, PhD, Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity
Contributor Information and Disclosures

Updated: Jun 18, 2008

Introduction

Background

Acquired partial lipodystrophy, also known as Barraquer-Simons syndrome or cephalothoracic lipodystrophy, is one of the rare forms of lipodystrophy. Mitchell initially reported this variety in 1885.¹ Barraquer and Simons further characterized the syndrome at the beginning of the 20th century. Since then, approximately 250 cases have been reported in English literature.

Acquired partial lipodystrophy usually begins in childhood, at a median age of 7 years.² It predominantly affects females and often follows an acute febrile illness. Fat loss is usually limited to the face, trunk, and upper extremities. Simultaneously, fat hypertrophy occurs in the lower extremities. These patients may develop nephropathies. Activation of alternate complement pathway has been demonstrated in most patients.

Compared with other types of lipodystrophy, acquired partial lipodystrophy is seldom associated with insulin resistance and its related metabolic derangements. This may be related to the fact that in this syndrome, patients have limited fat loss.

Disorders associated with acquired partial lipodystrophy include the following:

• Membranoproliferative glomerulonephritis -  This condition has been reported in about 20% of cases, and proteinuria, in 45% of cases. However, it is possible that other concomitant diseases (eg, urinary tract infection, diabetes) contribute to the rates of proteinuria.² Patients with membranoproliferative glomerulonephritis are more likely to have low C3 levels and the presence of C3 nephritic factor (C3NeF).^3,4,5
• Autoimmune diseases - Systemic lupus erythematosus is the most common of these^3,4 ; other reported autoimmune diseases include, but are not limited to, the following:
  
  
  • Dermatomyositis
  • Pernicious anemia
  • Celiac disease
  • Dermatitis herpetiformis
  • Rheumatoid arthritis
  • Temporal arteritis
  • Leukocytoclastic vasculitis
• Propensity to bacterial infections
• Other - POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal component, skin changes) syndrome,⁶ mental retardation, and retinal disease are among the syndromes that also are associated with acquired partial lipodystrophy.
• Diabetes and impaired glucose tolerance - In contrast with their occurrence in most other lipodystrophies, diabetes and impaired glucose tolerance are found only rarely in acquired partial lipodystrophy, being reported in 6.7% and 8.9% of patients, respectively.²

Pathophysiology

The precise pathophysiology of fat loss is unclear. Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated.⁷ C3 hypocomplementemia likely contributes to the association of this syndrome with autoimmune diseases and with a propensity for patients to acquire bacterial infections.² Other proposed mechanisms include an autoimmune process and genetic associations.^8,9

Frequency

United States

Approximately 250 cases have been reported since the recognition of this syndrome. It is a rare syndrome with no known prevalence, although it is more common than the generalized form of acquired lipodystrophy (Lawrence syndrome).²

International

Several case reports, coming from different parts of the world, have been made. However, the international incidence and prevalence of this disease are not known.

Mortality/Morbidity

Estimating the mortality rate based on the available literature is difficult. Several case reports have revealed an association between acquired partial lipodystrophy and other diseases (see the list of disorders associated with acquired partial lipodystrophy).

• Nephropathy, in the form of membranoproliferative glomerulonephritis, occurs in approximately 20% of patients.²
• Usually, patients do not have clinically evident renal disease or abnormalities in renal function until they have had the disease for 8 or more years.
  
  
  • Membranoproliferative glomerulonephritis usually presents with asymptomatic proteinuria or hematuria.
  • The disease may gradually progress. About 40-50% of patients develop end-stage renal disease over the course of 10 years. This condition is responsible for most recurrent hospital admissions in patients with acquired partial lipodystrophy.²
  • Rapid progression of renal disease in a pregnant patient was reported.¹⁰  
  • Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations.^11,12
• Associated autoimmune diseases (eg, systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population.
• Although uncommon, insulin resistance increases cardiovascular risk.
• Susceptibility to bacterial infections probably results from a C3 deficiency (due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial killing.

Race

No clear relationship exists between incidence and race in this syndrome; however, most reported patients have been of European descent.

Sex

Women are affected approximately 4 times more often than men.²

Age

The median age of onset of lipodystrophy has been reported to be around 7 years; however, onset occurring as late as the 4th or 5th decade of life also has been reported.²

The median age at presentation has been about 25 years, and women have been found to present later than men (age 28 y vs 18 y).

Clinical

History

• The problem usually begins in childhood. In most reports, disease onset occurs when patients are younger than 16 years.
• The onset usually follows an acute, febrile viral illness, most commonly measles. Minor surgical procedures and psychological stress have also been reported before the onset of fat loss.
• Lipodystrophy progresses slowly and occurs over a period of a few months to 2 years. Seventy-five percent of patients have been found to have significant fat loss when younger than 13 years.
• Acquired partial lipodystrophy is characterized by a fat loss that spreads through the cephalocaudal distribution from the face, neck, shoulders, arms, and forearms and that extends to the thoracic region and upper abdomen. Occasionally, fat loss may involve the groin or thighs. The hips and legs are usually spared (see Image 1). After puberty, women have a tendency to accumulate fat (lipohypertrophy) disproportionately in the hips and legs.¹³
• The process does not affect patient growth, and children usually experience developmental milestones with no difficulties. No pain is associated, but patients may occasionally complain of muscle weakness.
• Patients with acquired partial lipodystrophy do not usually experience the metabolic abnormalities observed in persons with other forms of lipodystrophy. However, inquiring about a history of menstrual irregularities, hirsutism, diabetes mellitus, and dyslipidemia is important, because metabolic abnormalities have been reported in these patients, and therapeutic interventions are available for these diseases. In addition, looking for evidence of renal disease, which occurs in approximately 20% of patients, is essential. Most patients are asymptomatic until the development of advanced renal impairment or acute decompensation.²
• Hepatomegaly has been reported in over 60% of patients. However, this finding might be due to associated autoimmune diseases.
• Patients with acquired partial lipodystrophy may present with a history that is suggestive of autoimmune or rheumatologic disease.

Physical

Patients usually have normal growth and secondary sexual characteristics. No specific bony abnormalities are present. 

• General inspection may reveal features of one of the associated autoimmune diseases (see the list of disorders associated with acquired partial lipodystrophy). Hepatomegaly might be present. Acanthosis nigricans and increased skin tags are very rare; they indicate the presence of insulin resistance.
• Exposing the patient properly for examination is very important; otherwise, the diagnosis can be easily missed. The best exposure during examination is achieved when the patient wears a gown exposing the extremities and trunk.
• These patients usually have characteristic body changes, including loss of fat and deposition of fat.
  • Loss of fat occurs in the face (around the cheeks and temples; eg, sunken cheeks), neck, shoulders and upper extremities, and upper abdomen. Breasts may lose fat and consist only of firm glandular tissue. Prominent veins in the arms with a muscular appearance (not associated with heavy exercise or muscle-building routines) are very characteristic of this syndrome.
  • Fat deposits can occur in the hips, lower extremities, breasts (in men and women), or other scattered areas around the body. These patients do not have cushingoid features.

• Gradual loss of subcutaneous fat in face, neck, trunk, and upper extremities occurring during childhood or adolescence (essential)
• Normal or excess subcutaneous fat in the hips and lower extremities
• Proteinuria or biopsy-proven membranoproliferative glomerulonephritis
• Low C3 level, reported in about 70% of patients (the C3 level might be normal with an elevated C3 degradation product, C3d)
• Presence of C3NeF, a polyclonal immunoglobulin G (IgG), able to break down C3 in normal human serum (it is reported to be present in about 80% of patients)
• Absence of other metabolic derangement
• Characteristic fat distribution, as measured by skinfold thickness or images from magnetic resonance imaging (MRI) studies^9,14
• Presence of autoimmune disease

Causes

Proposed mechanisms include the activation of an alternate complement pathway, autoimmune diseases, genetic associations, and idiopathic disease.

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