Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis, and obesity. Hyperlipoproteinemia type I (238600) and a disorder which closely simulates it, apolipoprotein C-II deficiency (207750), are characterized in part by hypertriglyceridemia; these disorders are ... Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis, and obesity. Hyperlipoproteinemia type I (238600) and a disorder which closely simulates it, apolipoprotein C-II deficiency (207750), are characterized in part by hypertriglyceridemia; these disorders are caused by mutations in the LPL (609708) and APOC2 (608083) genes, respectively. The hypertriglyceridemia in the cld mouse (see later) is characterized by severe chylomicronemia that is caused by LPL deficiency and exacerbated by partial deficiency of hepatic triglyceride lipase (HTGL; 151670). The mutation, however, affects neither the LPL nor the HTGL genes, but a transmembrane protein designated Lmf1 by Peterfy et al. (2007). To investigate the potential role of the LMF1 gene in human disease, Peterfy et al. (2007) screened 11 individuals with hypertriglyceridemia and decreased lipase activity for mutations. They identified a 48-year-old woman carrying a LMF1 mutation in homozygosity in whom severe hypertriglyceridemia was first noted at age 18 years. She had her first attack of pancreatitis at age 27, and had had at least 15 subsequent attacks. She began to develop lipodystrophy at age 44 that progressed to complete involvement of limbs and buttocks, sparing her face and abdomen. Also at age 44, type 2 diabetes was diagnosed, which was controlled with metformin. Bilateral large tuberous xanthomas on elbows, knees, and feet were present. Even in compliance with strict dietary fat restrictions, triglyceride concentration was 7 times the average of 31 control subjects at the lowest measurement, and increased markedly to over 70 times the control value when diet was not regulated. The severe hypertriglyceridemia was found to be due to LPL deficiency, as determined by a 93% decrease in LPL activity in the plasma of the affected individual. In addition, hepatic lipase activity was decreased by half, confirming the status of combined lipase deficiency.
In a patient with combined deficiency of lipoprotein lipase and hepatic lipase, concomitant hypertriglyceridemia, and associated disorders, Peterfy et al. (2007) detected homozygosity for a premature termination mutation in the LMF1 gene (611761.0001). The authors considered LMF1 to ... In a patient with combined deficiency of lipoprotein lipase and hepatic lipase, concomitant hypertriglyceridemia, and associated disorders, Peterfy et al. (2007) detected homozygosity for a premature termination mutation in the LMF1 gene (611761.0001). The authors considered LMF1 to be an important candidate gene in hypertriglyceridemia through its profound effect on lipase activity.