Köbberling Type of Familial Partial Lipodystrophy

An underrecognized syndrome

  1. Karen L. Herbst, MD, PHD1,
  2. Lisa R. Tannock, MD1,
  3. Samir S. Deeb, PHD1,
  4. Jonathan Q. Purnell, MD2,
  5. John D. Brunzell, MD1 and
  6. Alan Chait, MD1
  1. 1Department of Medicine, University of Washington, Seattle, Washington
  2. 2Department of Medicine, Oregon Health & Science University, Portland, Oregon

    Abstract

    OBJECTIVE—The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought.

    RESEARCH DESIGN AND METHODS—Fasting glucose, plasma lipids, leptin, HbA1c, and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes.

    RESULTS—Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-γ.

    CONCLUSIONS—FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease.

    Footnotes

    • Address correspondence and reprint requests to Karen L. Herbst, MD, PhD, Charles R. Drew University, Division of Endocrinology, Room 3069, Third Floor, 1731 East 120th St., Los Angeles, CA 90059. E-mail: kaherbst{at}cdrewu.edu.

      Received for publication 24 October 2002 and accepted in revised form 2 March 2003.

      A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

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