Familial hypobetalipoproteinemia and liver steatosis.

INTRODUCTION: The familial hypobetalipoproteinemia (FHBL) is an autosomal codominant disorder characterized by low total cholesterol (TC) and apolipoprotein B (apoB) levels. Its prevalence in the western population is evaluated 1:1000-1:3000. The basic defect rely in the apoB gene mutations. The clinical phenotype is heterogeneous ranging from fat malabsorption to achantocytosis, ataxia and visual impairment; more recently liver steatosis has been linked with the disease. So far the heterozygous condition is difficult to be diagnosed.AIMS & METHODS: The aim of the study was to examine patients affected by FHBL to evaluate the lipidic pattern and to detect liver steatohepatitis.21 subjects were recruited for the presence of TC < 5th percentile or because they were 1st degree relatives of the probands. Everyone was submitted to analysis to exclude secondary hypocholesterolemia and to check the presence and the nature of FHBL’s clinical manifestations.Lipoprotein profile was performed by density gradient ultracentrifugation, and the research of truncated apoBs was realized by Southern blot analysis. RESULTS: In 7/21 patients the presence of abnormally low LDL levels, the absence of diseases to which hypobetalipoproteinemia was secondary and the detection of a similar pattern in a first degree relative allowed the diagnosis of heterozygous FHBL; 3, out of 7, were children. In one additional case the diagnosis of FHBL was established by the detection of a new apoB truncated protein named apoB32,4. In 6/8 affected subjects (3/3 children) hepatic echotomography revealed fatty liver, in some cases associated with the elevation of aminotransferase. Hepatic cirrhosis was present in one case. The subject carrying apoB32,4 had been presenting since infancy abdominal pain and diarrhoea following fat ingestion CONCLUSION: Liver steatosis results well represented in the present study, since childhood in some cases. Fatty liver in this FHBL subjects most likely results from the reduced synthesis of truncated B apoproteins and from the inability of apoBs to export lipids from hepatocytes into the blood stream. The evolution of fatty liver in FHBL is unknown. Moreover the lenght of truncated apoB32,4 is suggestive of impaired lipids export from enterocytes: further investigations on fat absorption in the patient carrying this mutation are required. FHBL should be taken into consideration when unexplained fatty liver is present in subjects with low plasma cholesterol levels.