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Aug 18, 2026, 16:41

Mendel Roth: Partial Lipodystrophy as a Cause of Severe Hypertriglyceridemia

Mendel Roth, Lead Scientist at GBinsight/GB HealthWatch, shared a post on LinkedIn:

“Partial lipodystrophy as a cause of severe hypertriglyceridemia (sHTG)

An underappreciated monogenic cause of sHTG is familial partial lipodystrophy (FPLD).

In people with sHTG and recurrent pancreatitis, the differential diagnosis often focuses on familial chylomicronemia syndrome (FCS). However, FPLD is substantially more prevalent (estimated 1 in 15,000, PMID: 42001615) and is usually inherited in an autosomal dominant manner. By contrast, FCS is inherited in an autosomal recessive manner with an estimated prevalence of 1 in 250,000.

FPLD can phenocopy FCS with severe hypertriglyceridemia and pancreatitis, but the underlying biology is different.

In FPLD, dysfunctional adipose tissue produces severe insulin resistance, ectopic lipid deposition, diabetes, and sHTG.

As summarized in the table below, the two major genetic subtypes (accounting for 98percent of cases, PMID: 42001615) are FPLD2 (Dunnigan type), caused by pathogenic LMNA variants, and FPLD3, caused by pathogenic PPARG variants.

Take home: FPLD3, the more common subtype, can readily be misdiagnosed as FCS due to severe metabolic dysfunction characterized by sHTG with acute pancreatitis and relatively mild fat loss in the extremities that may be missed on clinical exam (PMID: 36397776). Treatment for FPLD is currently focused on managing symptoms. The leptin analog, metreleptin, is approved in Europe for FPLD and is undergoing clinical evaluation in the US.”

Mendel Roth: Partial Lipodystrophy as a Cause of Severe Hypertriglyceridemia