Multifactorial chylomicronemia syndrome (MCS) is a complex disease including a genetic component and the presence of lifestyle-related risk factors. We hypothesized that, in subjects with MCS, there would be a greater decrease in plasma triglycerides (TG) with a low-fat (F) diet than with a low-carbohydrate (C) diet. In secondary analyses, we tested the effect of both diets on TG concentration according to the presence or absence of a rare variant in the LPL gene. This randomized crossover dietary intervention included 12 adult subjects with MCS. Subjects followed 2 isocaloric diets, low-C (C, 35%; F, 45%) and low-F (F, 20%; C, 60%), in random order. Each diet lasted 3 weeks, followed by a 6-hour test meal. Diets were separated by a 2-week washout period. TG concentration in fasting subjects decreased by 55% during low-F diet (P = .002) and by 48% during low-C diet (P = .005). The difference between the 2 diets was not significant. However, we observed a more pronounced decrease in TG concentration (65% ± 17%) with the low-F diet compared with the low-C diet (46% ± 31%) (P = .06) in subjects carrying a rare variant in the LPL gene. This is the first study to show that dietary intervention is effective in MCS subjects. In addition, we highlighted the importance of the genetic profile in the choice of treatment by suggesting that subjects with a rare variant of the LPL gene have a greater reduction of TG concentration with a low-F diet than with a low-C diet.

Familial hypertriglyceridemia is a rare autosomal recessive inborn error of metabolism. Mutation within the LPL gene constitutes the first cause of monogenic etiology. Lipoprotein lipase (LPL) is the key enzyme in triglyceride-rich lipoproteins catabolism. Familial LPL deficiency is expressed by eruptive xanthomatosis and acute pancreatitis. We report a Moroccan case with a monstrous hypertriglyceridemia caused by LPL gene mutation. We discuss pathophysiology aspects according to available investigations data and the relevance of familial screening. The proband is a 19-year-old woman originating from the village of Taourirt (South of Morocco). She was admitted in emergency for diabetic ketoacidosis. Clinical investigations and routine laboratory tests were performed upon admission. Then lipoprotein electrophoresis and sequencing of the LPL gene were practiced. A monstrous hypertriglyceridemia up to 199 mmol/L was found. Lipoprotein electrophoresis has objectified profound disturbances on chylomicrons, VLDL and IDL. The sequencing detected a missense mutation p.S286R at homozygous state in a consanguinity context. Discovery of this LPL gene mutation is the first indigenous and documented case, never related in any other ethnic group. It constitutes a novel proof of a founder effect in the south Moroccan population. Prevalence studies with familial screening should be done for preventative action which is the only acceptable way to limit the cardiovascular and pancreatitis risks in this population where inbreeding is a general rule.