Journal zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Hepatology 2000; 33: 361-370 Printed in Denmark AN rights reserved Munksgaard . Copenhagen Copyright 8 European Association the Study of Liver Journal A study of fatty liver disease and plasma lipoproteins in a kindred with familial hypobetalipoproteinemia due to a novel truncated form of apolipoproteinB (APO B-54.5) Patrizia Tarugl ‘l*, Amedeo Lonardo2*, Giorgia Ballarini ’ , Laura Erspamer’, Emilio Tondelli3, Stefano Bertolini4 and Sebastian0 Calandra’ ‘Dipartimento di Scienze Biomediche, Universitri di Modena, ‘Divisione di Medicina Interna e Gastroenterologia, Ospeaizle Civile, Modena, ‘Servizio di Radiologia, Ospedale Civile. Modena, and 4Dipartimento di Medicina Interna, Universitci di Genova, Italy Background/Aims Familial hypohetalipoproteinemia fibrosis. He was heterozygous for a novel non-sense (FHBL) is a co-dominant disorder characterized by mutation of apo B gene producing a truncated apo B of reduced plasma levels of low-density lipoproteins. It 2745 amino acids (designated apo B-54.5, having half can he caused by mutations in the gene encoding apo- the size of normal apo B-100). Seven other members of lipoprotein B-100 (apo B), leading to the formation of his kindred carried apo B-54.5. Although all of them truncated apo Bs which have a reduced capacity to were hypolipidemic, their lipid levels showed a large in- export lipids from the hepatocytes as lipoprotein con- ter-individual variability not accounted for by poly- stituents. Case reports suggest the occurrence of liver morphisms of genes involved in apo B metabolism. Four disease in FHBL, but there are no studies of liver in- carriers (two heavy drinkers and two teetotallers), ir- volvement in FHBL with defined apo B gene muta- respective of their plasma lipid levels, had ultrasono- tions. The presence of fatty liver disease was investi- graphic evidence of fatty liver. In the other four carriers gated in a large FHBL kindred. no evidence of fatty liver was found. Methods: Plasma lipoprotein and apolipoprotein analysis, liver function tests, and apo B gene sequence were performed in 16 members of a FHBL kindred. The presence of fatty liver was assessed by ultrasound and computed tomography scanning. Results: The proband, a non-obese heavy drinker male with hypobetalipoproteinemia, had steatohepatitis with Conclusions: In this kindred apo B-54.5 predisposes to fatty liver, which however may require some ad- ditional factors to become clinically relevant. Key words: Alcohol; CT scanning; Fatty liver disease; Hypocholesterolemia; Steatohepatitis; Truncated apo B; Ultrasonography. zyxwvutsrqponmlkjihgfedcbaZYXWVUTS 0 BSERVATIONAL studies and clinical trials have sug- gested that individuals with hypocholesterolemia have a lower than average risk of developing cardio- vascular disease but apparently a higher risk for other diseases such as hemorrhagic stroke, cancer and other non-cardiovascular diseases when compared to sub- jects with higher cholesterol levels (l-8). However, there are no prospective studies on the impact, if any, Received 15 July 1999; revised 18 January; accepted 8 February 2000 Correspondence: Patrizia Tarugi, Dipartimento di Scienze Biomediche, Universita di Modena, Via Campi 287, I-41100 Modena, Italy. Tel. 39 059 428 613/428 629. Fax. 39 059 428 623. e-mail tarugi@unimo.it *The first two authors contributed equally to this work. of long-lasting primary hypocholesterolemia (primary low cholesterol syndromes) on human pathophys- iology. The primary low plasma cholesterol syndromes con- sist of several genetic disorders of plasma lipoproteins containing apolipoprotein B (9) such as: a) abetalipo- proteinemia, a rare recessive autosomal disease, associ- ated with defects of the microsomal triglyceride trans- fer protein (MTP), which plays a crucial role in the assembly of apo B-containing lipoproteins in liver and intestine (10); b) the chylomicron retention disease, a rare autosomal recessive disorder of unknown etiology (11); c) familial hypobetalipoproteinemia (FHBL), a relatively more frequent condition which co-segregates as a co-dominant phenotype and is associated with de- 361