Acquired Partial Lipodystrophy
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Lipodystrophy refers to the loss of adipose tissue. It is classified as either diffuse (generalized) or local (partial) and results from either genetic or acquired etiologies. Ectopic fat in tissues such as liver and muscle may be increased. The cumulative loss of fat leads to a decrease in adipose-derived adiponectin and leptin. Circulating levels of these adipokines are lower in generalized versus partial lipodystrophy as predicted from the loss of fat. [1, 2]
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. [3] 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. [4] 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. The phenotype can be variable and sometimes only affecting the face. [5]
Compared with other types of lipodystrophy, acquired partial lipodystrophy is seldom associated with insulin resistance and its related metabolic derangements. [6] 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. [4] Patients with membranoproliferative glomerulonephritis are more likely to have low C3 levels and the presence of C3 nephritic factor (C3NeF). [7, 8, 9]
Autoimmune diseases – Systemic lupus erythematosus is the most common of these [7, 8] ; other reported autoimmune diseases include, but are not limited to, the following:
Pernicious anemia
Celiac disease
Dermatitis herpetiformis
Temporal arteritis
Leukocytoclastic vasculitis
Propensity to bacterial infections
Other – POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal component, skin changes) syndrome, [5] 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. [4]
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. [11, 12] C3 hypocomplementemia likely contributes to the association of this syndrome with autoimmune diseases and with a propensity for patients to acquire bacterial infections. [4] Other proposed mechanisms include an autoimmune process, viral infection, [13] and genetic associations. [14, 15, 16]
Recently novel mutations in the LMNB2 gene have been identified in 4 of 5 acquired partial lipodystrophy patients tested. [14, 17] A related gene, LMNA, has coding mutations associated with another form of lipodystrophy, Dunnigan-type familial partial lipodystrophy. [18, 19]
Another form of lipodystrophy that fits the classification of “acquired partial” not involving the complement pathway is associated with hematopoietic stem cell transplantation (HSCT) to treat leukemia or neuroblastoma. Five cases were reported but the phenotype resembles Dunnigan-type familial partial lipodystrophy rather than classic acquired partial lipodystrophy. [20]
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). [4]
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.
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. [4]
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. [4] Rapid progression of renal disease in a pregnant patient was reported. [21] Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations. [22, 23]
Associated autoimmune diseases (eg, systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population. Localized scleroderma has also been reported. [24]
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.
No clear relationship exists between incidence and race in this syndrome; however, most reported patients have been of European descent.
Women are affected approximately 4 times more often than men. [4]
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. [4]
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).
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George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society
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Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society
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George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society
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Amir E Harari, MD Staff Physician, Endocrinology Division, Instructor, Department of Clinical Medicine, Naval Medical Center at San Diego
Amir E Harari, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, American College of Physicians, Endocrine Society
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Waleed Aldhahi, MD, FRCPC Clinical Research Fellow, Department of Endocrinology, Joslin Diabetes Center, Harvard University
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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
Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society
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Irina Lendel, MD Clinical Instructor in Endocrinology, Division of Endocrinology, Diabetes, and Metabolism, Milton S Hershey Medical Center
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Acquired Partial Lipodystrophy
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