BRAIN AND SKELETAL-MUSCLE BIOENERGETIC FAILURE IN FAMILIAL HYPOBETALIPOPROTEINEMIA

Objective-To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia. Methods-B rain and skeletal muscle bioenergetics were studied by in vivo phospho rus MR spectroscopy (P-31-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindre d with familial hypobetalipoproteinaemia. Plasma concentrations of vit amin E and coenzyme Q(10) (CoQ(10)) were also assessed. Results-Brain P-31-MRS disclosed in all patients a reduced phosphocreatine (PCr) con centration whereas the calculated ADP concentration was increased. Bra in phosphorylation potential was reduced in the members by about 40%. Skeletal muscle was studied at rest in the three members and during ae robic exercise and recovery in the son and daughter. Only the mother s howed an impaired mitochondrial function at rest. Both son and daughte r showed an increased end exercise ADP concentration whereas the rates of postexercise recovery of PCr and ADP were slow in the daughter. Th e rate of inorganic phosphate recovery was reduced in both cases. Plas ma concentration of vitamin E and CoQ(10) was below the normal range i n all members. Conclusions-Structural changes in mitochondrial membran es and deficit of vitamin E together with reduced availability of CoQ( 10) can be responsible for the multisystemic bioenergetic deficit. Pre sent findings suggest that CoQ(10) supplementation may be important in familial hypobetalipoproteinaemia.