Context: Sporadic hyperchylomicronemia (type V hyperlipoproteinemia) results from complex interactions between genetic and environmental factors that often remain unknown.
Design: Upon investigation of a patient suffering from recurrent hypertriglyceridemic pancreatitis without family history or conventional secondary cause of dyslipidemia, we identified a previously unreported nonsense heterozygous lipoprotein lipase (LPL) gene mutation S172fsX179 associated with an antihuman LPL IgG.
Results: This autoantibody partially inhibited wild-type LPL activity in vitro. Furthermore, the patient's plasma triglyceride concentrations were efficiently decreased under immunosuppressive treatment, and this was confirmed by sequential withdrawal/reintroduction tests.
Conclusions: We consider that this unique combination of a genetic defect and an autoimmune disease results in chronic major hypertriglyceridemia. Because immunosuppressive treatment can improve this dyslipidemia, assessment of anti-LPL autoantibody is worthwhile in unmanageable chronic major hypertriglyceridemia, even in the presence of a heterozygous LPL deficiency.