Brain and skeletal muscle bioenergetic failure in familial hypobetalipoproteinaemia.

Abstract

Objective-To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia. Methods-Brain and skeletal muscle bioenergetics were studied by in vivo phosphorus MR spectroscopy (31P-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindred with familial hypobetalipoproteinaemia. Plasma concentrations of vitamin E and coenzyme Q,0 (CoQ,0) were also assessed.Results-Brain 31P-MRS disclosed in all patients a reduced phosphocreatine (PCr) concentration whereas the calculated ADP concentration was increased. Brain phosphorylation potential was reduced in the members by about 40%. Skeletal muscle was studied at rest in the three members and during aerobic exercise and recovery in the son and daughter. Only the mother showed an impaired mitochondrial function at rest. Both son and daughter showed an increased end exercise ADP concentration whereas the rates of postexercise recovery of PCr and ADP were slow in the daughter. The rate of inorganic phosphate recovery was reduced in both cases. Plasma concentration of vitamin E and CoQ,, was below the normal range in all members. Conclusions-Structural changes in mitochondrial membranes and deficit of vitamin E together with reduced availability of CoQ,0 can be responsible for the multisystemic bioenergetic deficit. Present findings suggest that CoQ,0 supplementation may be important in familial hypobetalipoproteinaemia. (7 Neurol Neurosurg Psychiatry 1997;62:574-580) The pathogenesis of this disorder is not yet fully understood. However, neurological symptoms and signs and the underlying neuropathological changes have been related to altered composition of cellular membranes due to the deficit of lipoprotein and vitamin E found in these patients34 and to the inability of the liver to incorporate vitamin E in the very low density lipoprotein and in LDL.5 A deficit of vitamin E leads to an excessive lipid peroxidation with production of lipid peroxyl radicals which in turn can result in damage to cell membranes36 as well as proteins and DNA.78 Therefore, it is conceivable that by different mechanisms, the damage due to free radicals results in an impairment of mitochondrial functionality and ATP production.9 12 Tissue bioenergetics can be assessed in vivo by phosphorus magnetic resonance spectroscopy (31P-MRS), the only available noninvasive method that gives precise information on the efficiency of ATP production and the extent to which oxidative metabolism meets the bioenergetic needs of cell function.The aim of this study was to investigate by in vivo 31P-MRS whether a multisystemic defect of tissue bioenergetics is an underlying feature of the neurological disorders found in patients with a deficit of APO-B.In view of the antioxidant role of vitamin E and the bioenergetic and antioxidant functions of CoQ,0,7 13 we also assessed the plasma concentrations of vitamin E and CoQ,0.Patients and methods PATIENTS AND LABORATORY DATA Figure 1 shows the famil...

Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia

“…Vitamin E is a lipid-soluble antioxidant that localizes in membranes, including mitochondrial membranes (31), and protects against both lipid peroxidation (31, 32) and mtDNA damage (32). The connection with mitochondrial respiratory chain dysfunction is highlighted further by the fact that vitamin E deficiency can lead to mitochondrial damage as illustrated in a report of a deficit of brain and skeletal muscle respiration in a family with vitamin E deficit associated with hypobetalipoproteinemia (33) and in a rat model of vitamin E deficiency (34).…”

Elevated Hydroperoxide Levels and Antioxidant Patterns in Papillon‐Lefèvre Syndrome

“…CoQ is increasingly considered as one of the most efficient non-enzymatic antioxidants of biomembranes alongside vitamin E. 47,48 Unlike vitamin E, which is an essential constituent of many foods, CoQ is synthesized in all living systems especially for bioenergetic reasons, but it has been shown that CoQ can amplify the antioxidant capacity of vitamin E by reactivating its antioxidant reaction product 49 or that it is an essential co-antioxidant in the maintenance of lipoprotein integrity against oxidative insult. 50 Low plasma CoQ levels have been demonstrated in several pathologies, 51,52 and it is considered one of the valuable markers for evaluating the overall antioxidant capacity of plasma.…”

Oxidative Injury and Inflammatory Periodontal Diseases : the Challenge of Anti-Oxidants to Free Radicals and Reactive Oxygen Species

“…The investigations carried out by Battino and co-workers (Battino et al, 1991a(Battino et al, ,b, 1993(Battino et al, , 1997aHuertas et al, 1991;Ferri et al, 1994;Quiles et al, 1994;Atleva et al, 1995;Littarru et al, 1996;Armeni et al, 1997;Lodi et al, 1997;Mataix et al, 1997) (Kagan et al, 1996).…”