A tale of 2 cousins: An atypical and a typical case of abetalipoproteinemia

Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by mutations of the MTTP gene. This disease is characterised by a defect in the lipidation of APO B and the absence of VLDL and chylomicron production. Patients affected by ABL present neurological, hemalogical and gastro-intestinal symptoms due to deficiency in lipophilic vitamins and fat malabsorption. We herein report the case of two cousins, one presenting classical symptoms of abetalipoproteinemia and one presenting a much attenuated phenotype. The proband carried a novel combination of MTTP mutations, the 1867+1G>A and the R540C mutations. This patient never received any vitamin supplements and was relatively free of symptoms despite an undetectable APO B concentration. Her cousin was homozygous for 1867+1G>A MTTP mutation and presented most of the classical symptoms of ABL. In conclusion we report a very unusual kindred where on affected member is strongly symptomatic of ABL whereas the other presents very mostly asymptomatic disease suggesting that ABL can present itself with a very incomplete clinical penetrance.