Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia.

Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are genetic diseases characterized by low density lipoprotein deficiency. ABL presents early in life with the gastroenterological manifestations of fat malabsorption, steatorrhea, and failure to thrive, and later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A and E. Heterozygous FHBL subjects are usually asymptomatic, but may develop fatty liver disease. In homozygous (compound heterozygous) FHBL, the clinical and biochemical features are indistinguishable from those of ABL and treatment recommendations are the same: dietary fat restriction to prevent steatorrhea, and long-term high-dose vitamin E and A supplementation to prevent or at least slow the progression of neuromuscular and retinal degenerative disease. Despite their low plasma vitamin E levels, individuals with heterozygous FHBL do not require vitamin E supplementation. There are conflicting reports on whether increased oxidative stress is seen in ABL; these differences may relate to the small size of patient groups as well as differences in patient age and dose of vitamin E supplementation, or the contribution from dietary sources of vitamin E. High density lipoproteins in ABL appear to be severely oxidized yet able to inhibit platelet aggregation by binding to scavenger receptor B1. We review the role of vitamin E and oxidative stress in ABL and FHBL.

Liver fibrosis in a patient with familial homozygous hypobetalipoproteinaemia: possible role of vitamin supplementation.

A case of apolipoprotein B-related disorder is reported in which liver fibrosis developed without long term administration of medium chain triglycerides, previously incriminated in the pathogenesis of this lesion. The patient was a young woman in whom the diagnosis of familial homozygous hypobetalipoproteinaemia was made at the age of 21. A first liver specimen taken at diagnosis revealed steatosis, hypertrophic Golgi apparatus and proliferating smooth endoplasmic reticulum. The patient was treated with vitamin A and E supplementation only. Two years later, a second liver biopsy, carried out because of increased serum alanine aminotransferase concentrations, showed fibrosis, mild cytolysis and marked mitochondrial alterations. Hepatic level of vitamin A was increased. This finding supports the hypothesis that liver disease observed in our patient might be an adverse effect of vitamin supplementation. Our observation underlines the importance of including liver function tests in the follow up of patients with apolipoprotein B-related disorders.