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Hypertriglyceridemia, low HDL and impaired fasting glucose with skinny arms and legs
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A 50-year-old woman was referred for severe mixed dyslipidemia. Her triglycerides have ranged between 1,500 mg/dL and 2,000 mg/dL and HDL between 18 mg/dL and 24 mg/dL. The dyslipidemia was first identified when she was an adolescent but has not been treated until recently. She has never had pancreatitis, is not on hormone therapy and does not consume alcohol. There is no personal or family history of cardiovascular disease. No one else in her family has dyslipidemia that she knows of.
Her primary care physician began fenofibric acid (Trilipix, Abbott Laboratories) 135 mg/day three weeks ago. He also noted impaired fasting glucose. He advised metformin, but she is not taking it. HbA1c is 6.3%.
The most striking physical exam finding is her almost complete lack of subcutaneous body fat, particularly in her arms, legs and torso. The muscles and blood vessels in her arms were easily visualized. However, there was increased fat deposition in her neck. She also reported unusual fat deposition around her genitalia.
Mixed dyslipidemia and IFG are commonly due to metabolic syndrome as a result of genetic predisposition combined with environmental factors. On occasion, however, we see other causes. This patient’s diagnosis is most likely type 2 familial partial lipodystrophy. She has no known family history but her family members rarely go to doctors. In addition, the diagnosis may be missed in men because they are often less severely affected than women.
Acquired lipodystrophy due to treatment of HIV is relatively common; genetic causes of generalized or partial lipodystrophy are seen less frequently. Familial partial lipodystrophy results in progressive loss of adipose tissue in the extremities. It is inherited in an autosomal dominant pattern and presents with onset of puberty. Familial partial lipodystrophy can result in hypertriglyceridemia, low HDL, insulin resistance and/or diabetes mellitus. Women may have menstrual irregularity or polycystic ovary syndrome. There appears to be increased risk of premature cardiovascular disease in some variants including type 2 familial partial lipodystrophy.
Familial partial lipodystrophy is divided into three forms: type 1 (Kobberling type), type 2 (Dunnigan type) and type 3. The genetic cause of type 1 is unknown. Type 2 familial partial lipodystrophy appears to be due to mutations in the LMNA gene encoding nuclear lamin A/C. The mechanism by which mutations of this gene cause adipocyte dystrophy and metabolic abnormalities is unclear. Type 3 familial partial lipodystrophy is due to mutations in the gene encoding peroxisome proliferator-activated receptor gamma.
I considered beginning thiazolidinediones because these agents have been shown to be effective in managing the diabetes and other metabolic abnormalities of lipodystrophy. Adding a statin would also be reasonable because type 2 familial partial lipodystrophy is associated with increased cardiovascular risk.
However, the patient does not have prescription drug coverage. Therefore, we will wait for results of follow-up laboratory studies before adding other medications.
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