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Disease Profile

Acquired generalized lipodystrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

E88.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Lawrence syndrome; Lawrence-Seip syndrome; Acquired lipoatrophic diabetes

Categories

Endocrine Diseases; Skin Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 79086

Definition
A rare lipodystrophic syndrome characterized by loss of adipose tissue, and is a syndrome of insulin resistance that leads to increased cardiovascular risk. Acquired generalized lipodystrophy is related to a selective loss of subcutaneous adipose tissue occurring exclusively at the extremities (face, legs, arms, palms and sometimes soles).

Epidemiology
More than 100 cases have been described and the female to male ratio is 3:1.

Clinical description
The clinical phenotype is similar to that of Berardinelli-Seip syndrome (see this term), but lipoatrophy appears secondarily during childhood, adolescence or adulthood, and as a result the syndrome is thought to be acquired. In some cases, loss of adipose tissue is localized, especially if it is preceded by a panniculitis. The syndrome is associated with a voracious appetite and an acceleration of growth in adolescents. One third of cases are accompanied by acanthosis nigricans and a polycystic ovary syndrome (see these terms). Hepatomegaly with steatosis and a risk of cirrhogenous progression is common. Biologically, hyperinsulinemia and insulin-resistant diabetes are observed, often associated with severe hypertriglyceridemia with low plasma levels of leptin and adiponectin. Proteinuria associated with focal segmental glomerulosclerosis or with membranoproliferative glomerulonephritis have been reported recently, as well as dysregulation of growth hormone. Three types of the disease have been described: 1) a form with panniculitis (inflammatory nodules followed by lipoatrophy), 2) an autoimmune form that is readily associated with other syndromes such as chronic active hepatitis, Hashimoto struma and hemolytic anemia, but also with dermatomyositis and Sjogren's syndrome (see these terms), 3) idiopathic.

Etiology
The cause of the disease remains unknown. There may be infectious triggering factors (there was a recent case of the panniculitis type that appeared after tuberculosis) or an autoimmune mechanism. A recent publication showed activation of the classical complement pathway (low C4). This is in contrast to acquired partial lipodystrophy (see this term) which affects the upper half of the body and is characterized by an activation of the alternative complement pathway (low C3). Progression towards partial lipoatrophy, focal or generalized, has been reported in patients with dermatomyositis, amongst whom this could be a late relapse, and it is more common that the antibody anti-p155 is present. The hypothesis of an underlying genetic factor has not been rejected.

Diagnostic methods
Diagnosis is clinical and should be confirmed by an assessment of body fat, in particular by biphotonic absorptiometry and magnetic resonance imaging.

Differential diagnosis
Differential diagnoses include other forms of extreme insulin resistance (Rabson-Mendenhall syndrome, leprechaunism, Berardinelli type lipodystrophy and insulin resistance syndromes types A and B; see these terms) and other lipodystrophies.

Management and treatment
The treatment of the metabolic manifestations is a priori no different to the treatment of other forms of insulin resistance: physical exercise, insulin sensitizers such as metformin or pioglitazone, insulin (or preferably insulin analogues), antihypertensives, and monitoring and treatment of hypertriglyceridemia. The efficacy of recombinant human leptin has been demonstrated on the metabolic level but this therapy is not available in all countries. In serious autoimmune forms of the disease, immunosuppressive therapy may be indicated.

Prognosis
The prognosis is not well known but is probably related to cardiovascular risk (linked to the insulin-resistance syndrome) and to the underlying cause of the disease.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Generalized lipodystrophy
0009064
80%-99% of people have these symptoms
Hyperinsulinemia
0000842
30%-79% of people have these symptoms
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Calf muscle pseudohypertrophy
0003707
Cardiomyopathy
Disease of the heart muscle
0001638
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Insulin-resistant diabetes mellitus
Insulin resistant diabetes
Insulin-resistant diabetes

[ more ]

0000831
Progeroid facial appearance
Premature aged appearance
0005328
5%-29% of people have these symptoms
Abnormality of complement system
0005339
Acanthosis nigricans
Darkened and thickened skin
0000956
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Acute pancreatitis
Acute pancreatic inflammation
0001735
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Generalized hirsutism
Excessive hairiness over body
0002230
Generalized hyperpigmentation
0007440
Hepatomegaly
Enlarged liver
0002240
Hypertension
0000822
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Myopathy
Muscle tissue disease
0003198
Panniculitis
Inflammation of fat tissue
0012490
Polycystic ovaries
0000147
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
1%-4% of people have these symptoms
Astrocytoma
0009592
Lymphoma
Cancer of lymphatic system
0002665
Unicameral bone cyst
0012064

Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • The NORD Physician Guide for Acquired generalized lipodystrophy was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.