The familial hypobetalipoproteinemia (FHBL) is an autosomal codominant disorder characterized by total cholesterol (TC), LDL-cholesterol(LDL-C), and apoprotein B (apoB) levels <5° percentile. The defect rely in apoB gene mutations codifying for truncated apoB, variably shorter than normal size (apoB100). The clinical phenotype is heterogeneous; fatty liver in adults is described, but the clinical presentation is not clear in pediatric age. The aim of the study was the evaluation of the clinical phenotype in FHBL patients in pediatric age. 8 FHBL families were submitted to analysis:16 cases, 8 of whom were children (age<14). The presence of low CT, LDL-C and apoB in 2 first degree relatives, the lipoprotein profile and Western blotting of apoB (performed after density gradient and sequential ultracentrifugation), and apoB gene sequencing allowed the diagnosis of heterozygous FHBL. Everyone was submitted to analysis to exclude secondary hypocholesterolemia and to check the presence and the nature of clinical manifestations, with standard methods. In 10/16 subjects echotomograpny revealed fatty liver, that was present in 2/8 children. Moreover, irritable bowel symptoms after rich fat meals ingestion were recurrent. In 3 families, 3 new apoB gene mutations were detected: 2 were deletions and one was a substitution, generating STOP codons at positions 1306, 1470 and 1509, and then causing respectively the synthesis of truncated apoB28,8, apoB32,4, and apoB39,6. Heterozygous FHBL is a primitive lipid metabolism disorder, that is probably underdiagnosed. The evolution of fatty liver in FHBL subjects is unclear, but cirrhosis and HC are described. So far is necessary to diagnose FHBL in pediatric age, to submit these patients to follow-up and therapy, if it is required.
Familial Hypobetalipoproteinemia and liver steatosis.
GUARDAMAGNA, Ornella
2003-01-01
Abstract
The familial hypobetalipoproteinemia (FHBL) is an autosomal codominant disorder characterized by total cholesterol (TC), LDL-cholesterol(LDL-C), and apoprotein B (apoB) levels <5° percentile. The defect rely in apoB gene mutations codifying for truncated apoB, variably shorter than normal size (apoB100). The clinical phenotype is heterogeneous; fatty liver in adults is described, but the clinical presentation is not clear in pediatric age. The aim of the study was the evaluation of the clinical phenotype in FHBL patients in pediatric age. 8 FHBL families were submitted to analysis:16 cases, 8 of whom were children (age<14). The presence of low CT, LDL-C and apoB in 2 first degree relatives, the lipoprotein profile and Western blotting of apoB (performed after density gradient and sequential ultracentrifugation), and apoB gene sequencing allowed the diagnosis of heterozygous FHBL. Everyone was submitted to analysis to exclude secondary hypocholesterolemia and to check the presence and the nature of clinical manifestations, with standard methods. In 10/16 subjects echotomograpny revealed fatty liver, that was present in 2/8 children. Moreover, irritable bowel symptoms after rich fat meals ingestion were recurrent. In 3 families, 3 new apoB gene mutations were detected: 2 were deletions and one was a substitution, generating STOP codons at positions 1306, 1470 and 1509, and then causing respectively the synthesis of truncated apoB28,8, apoB32,4, and apoB39,6. Heterozygous FHBL is a primitive lipid metabolism disorder, that is probably underdiagnosed. The evolution of fatty liver in FHBL subjects is unclear, but cirrhosis and HC are described. So far is necessary to diagnose FHBL in pediatric age, to submit these patients to follow-up and therapy, if it is required.
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