Barraquer–Simons syndrome

Overview

Barraquer–Simons syndrome, also known as acquired partial lipodystrophy (APL), is a rare disorder characterized by the progressive and symmetrical loss of subcutaneous fat, primarily from the upper body including the face, arms, and trunk. This fat loss is often accompanied by fat accumulation in the lower body and is frequently associated with complement system abnormalities and autoimmune diseases. First described by Barraquer in 1907 and later expanded by Simons in 1911, this condition typically begins in childhood or adolescence and is more common in females.

Causes

The exact cause of Barraquer–Simons syndrome is not fully understood, but it is believed to involve immune-mediated damage to adipose tissue. A key factor is the dysfunction of the complement system, particularly:

• Low serum complement component C3 levels

• Presence of C3 nephritic factor (C3NeF) – an autoantibody that stabilizes the alternative pathway C3 convertase, leading to continuous activation and consumption of complement proteins

• Genetic predisposition in some cases, though not inherited in a classical Mendelian pattern

• Association with autoimmune disorders such as systemic lupus erythematosus and membranoproliferative glomerulonephritis (MPGN)

Symptoms

The hallmark feature of Barraquer–Simons syndrome is the slow and progressive loss of fat from specific regions of the body, with varying systemic involvement:

• Progressive fat loss from the face, neck, arms, and upper torso

• Normal or increased fat deposition in the hips, buttocks, and legs

• Facial changes including a gaunt or hollowed appearance

• Proteinuria and hematuria – signs of kidney involvement, often due to MPGN

• Fatigue and weakness in some individuals

• Possible development of autoimmune symptoms

Diagnosis

Diagnosis of Barraquer–Simons syndrome is based on clinical presentation, laboratory findings, and exclusion of other causes of fat loss:

• Physical examination – showing characteristic regional fat loss pattern

• Complement testing – revealing low C3 levels and presence of C3NeF

• Kidney function tests and urinalysis – to detect renal complications such as MPGN

• Imaging studies – including MRI or CT scans to confirm fat distribution abnormalities

• Autoimmune workup – screening for coexisting conditions like lupus or dermatomyositis

Treatment

There is no cure for Barraquer–Simons syndrome, and treatment is aimed at managing symptoms and preventing complications:

• Monitoring and treatment of renal involvement – including blood pressure control and, in some cases, immunosuppressive therapy

• Immunosuppressive agents – such as corticosteroids or rituximab for autoimmune manifestations or nephropathy

• Cosmetic interventions – such as facial fillers or fat grafting to improve appearance and self-esteem

• Regular follow-up with nephrology and immunology specialists

Prognosis

The prognosis of Barraquer–Simons syndrome depends on the extent of systemic involvement, particularly renal complications:

• Fat loss is permanent and may progress slowly over years

• Renal disease such as membranoproliferative glomerulonephritis can impact long-term health and may require aggressive management

• Most individuals have a normal life expectancy with appropriate monitoring and management of complications

• Psychosocial support is important due to the visible nature of fat loss and its potential impact on mental health