Lipodystrophy syndromes are a rare group of heterogeneous disorders characterized by a lack of adipose tissue, which may seem counterintuitive to be included within the test content area of the ABOM. However, the inability to store fat means excess calories are stored in organs, leading to severe metabolic consequences, which is a prime target for the exam. A relatively shallow depth of knowledge is likely all that is required to master this content area, with the high-yield points summarized in this blog.

Lipodystrophies are phenotypically apparent by the significant lack of fat accumulation, or in some cases, the disproportionate locations of fat accumulation. The extent of fat loss and proportional leptin deficiency correlates with the severity of metabolic findings, which include diabetes, hypertriglyceridemia, metabolic dysfunction-associated steatotic liver disease, and their corresponding physical exam findings such as acanthosis nigricans, eruptive xanthomas, and hepatomegaly. Because subcutaneous adipose tissue is markedly reduced or absent, the underlying musculature and superficial veins become unusually prominent, producing a muscular or athletic appearance.

Although detailed knowledge of specific subtypes is not necessary, a general understanding of how these are categorized can help with diagnosis and determine eligibility for treatment with leptin replacement.

  • Congenital generalized: As the name suggests, this genetic condition is characterized by a near-complete absence of adipose tissue throughout the body that is apparent at birth or becomes evident during early childhood. Patients often appear unusually muscular due to the lack of subcutaneous fat and have markedly low or nearly absent leptin levels. Severe insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes commonly develop early in life.
  • Acquired generalized: Although it resembles congenital generalized lipodystrophy in appearance, this form typically develops later in childhood or adolescence. Rather than being inherited, it is thought to be autoimmune in origin and may be triggered by an inflammatory illness or other immune-mediated process. Patients develop progressive, generalized loss of subcutaneous fat and exhibit similar metabolic complications.
  • Familial partial: Typically presenting around puberty or during adolescence, this inherited form is characterized by progressive loss of subcutaneous fat from the limbs, buttocks, and trunk, with relative or excessive fat accumulation in the face, neck, and the abdominal region, often producing a “Cushingoid” appearance. Although leptin levels are often normal or only mildly reduced, patients commonly develop similar metabolic sequelae.
  • Acquired partial: Unlike familial partial lipodystrophy, this form is autoimmune rather than inherited. It is characterized by progressive loss of subcutaneous fat beginning in the face and upper body, while fat in the lower body is often preserved or even increased. Although metabolic complications can occur, they are generally less severe than in generalized forms. Renal disease, particularly membranoproliferative glomerulonephritis and abnormalities of the complement pathway, especially low C3 levels, are common associations.

The diagnosis of lipodystrophies does not require genetic testing; rather, it is based on the clinical presentation, physical examination, and family history. Laboratory testing is helpful for screening for underlying metabolic complications and chronic diseases, including a complete blood count and comprehensive metabolic panel to evaluate for metabolic dysfunction-associated steatohepatitis using the fibrosis-4 (FIB-4) index, with subsequent imaging (e.g., elastography) as indicated. Additional testing includes a hemoglobin A1c to assess for insulin resistance and a lipid panel to evaluate for hypertriglyceridemia and metabolic syndrome.

Treatment is focused on managing the associated metabolic complications, similar to patients without lipodystrophy, through lifestyle modifications and appropriate pharmacotherapy when indicated. However, because patients with congenital and acquired generalized lipodystrophy have marked leptin deficiency, they are eligible for treatment with the leptin replacement analog metreleptin. This treatment was FDA-approved in 2014 for patients with congenital or acquired generalized lipodystrophy to treat metabolic complications in conjunction with lifestyle modifications. Benefits include improvements in insulin resistance and hypertriglyceridemia, as well as normalization of pubertal development and growth in pediatric patients.

One additional form of lipodystrophy you should be familiar with is HIV-associated. This viral infection and, more commonly, older antiretroviral therapies can lead to a syndrome of abnormal fat redistribution characterized by peripheral lipoatrophy (face, limbs, and buttocks) with central fat accumulation (abdomen, dorsocervical fat pad, and breasts). Patients may also develop insulin resistance, dyslipidemia, and an increased risk of cardiovascular disease. Management focuses on optimizing antiretroviral therapy when appropriate and treating the associated metabolic complications.

If you are able to recognize a patient in a clinical vignette that matches the description of lipodystrophy, understand the underlying metabolic risks this condition leads to, and know that metreleptin is an approved therapy for the congenital and acquired generalized subtypes, you will likely have covered all that is needed for this rare condition. Review the table below, which summarizes the subtypes and their differentiating features:

Sample Question

A 7-year-old boy is brought to the clinic to establish care after moving to a new state. His parents report that he has appeared unusually muscular since infancy despite never participating in organized sports. On examination, he has a near-complete absence of subcutaneous fat throughout his body, prominent musculature, and hepatomegaly. Which of the following is most associated with this patient’s condition?

A. Hypertriglyceridemia and early-onset diabetes mellitus
B. Progressive sarcopenia due to peripheral nerve denervation
C. Hyperphagia with darkly pigmented skin after initiating treatment
D. Moderate intellectual disability with self-injuring behaviors
E. Progressive cerebellar ataxia and sensorineural hearing loss

Next Week: Special Populations with Obesity (Turner Syndrome, Achondroplasia, and Down Syndrome)

Upcoming: Monthly Knowledge Check: This is a review checklist of must-know items for ABOM exams based on the previous four blog topics. In addition, this will include a brief explanation of the correct answers to previous sample questions.

For more practice questions, check out the following:

  • Obesity Medicine Board Review Questions (2026): Q 39.
  • Obesity Medicine Practice Tests (2026): Q 179.

(Copyright 2026) Obesity Medicine Board Review Questions, LLC: obesitymedicinereview.com

Featured image: Modified from VectorStock (image license purchased)

Copyediting by Kelly Smith

Now available: A full line of ABOM study resources with 775+ challenging questions in a mobile or book format. Access to both formats is available in a discounted Ultimate Package, which also includes a Pass Guarantee (if you fail the exam in 2026, you get the 2027 edition free), 50 bonus questions released in August, and the newest book, Obesity Medicine: Sample Questions and Study Blogs, which includes all the updated previous study blogs in a paperback format. Check it out here!