Primary Hyperchylomicronemias in three patients from highly inbred ethnic groups: genetic and therapeutic aspects

During a genetic study of primary hypertriglyceridemias we analysed the genes encoding the enzyme lipoprotein lipase (LPL) and its activator the apolipoprotein C-II (apoCII) in 3 subjects with primary hypertriglyceridemia. Proband I, a 12 years-old boy, born from two first cousins from Morocco, had high plasma triglycerides (>2.000 mg/dl) associated with recurrent abdominal pain. The LPL gene sequence revealed that he was homozygous for a c.1032 T->A transversion in exon 7, which converts serine at position 259 into arginine (S259R). Although both parents and one sister were carriers of this mutation, only the father had hypertriglyceridemia. S259R substitution had been previously reported in hyperchylomicronemic patients of Berberian descent in Morocco. Proband II was a 11 months female from New-Zealand born from two second double-cousins of Maori descent. She had severe hypertriglyceridemia (>10.000 mg/dl) lipid infiltration of the retina and the central nervous system. LPL gene sequence was negative whereas the sequence of apo C-II gene revealed that she was homozygous for a c.1118 C->A transversion in exon 4 which converts the codon TAC (tyrosine at position 63) into TAA (stop) (Y63X). This new mutation results in a truncated apo C-II devoid of the LPL binding domain. This mutation introduces a new MseI restriction site; this allowed the rapid screening of the mutation in all family members. Proband III was a 5 year-old boy born from two first cousins from Morocco. The sequence of LPL and apo C-II genes in this case was negative indicating the presence of another gene affecting triglyceride metabolism. All subjects were treated with PUFA supplementation (3.4 g/day), obtaining a reduction (about 40%) of the triglycerides levels and a relief of the symptoms. Thus severe recessive hypertriglyceridemias due to rare mutations of LPL, apo C-II or other unknown genes are expected to occur in highly inbred ethnic groups and respond to the therapy with ω-3 fatty acids.