Heterozygous Familial Hypobetalipoproteinemia in Children and Adolescents: Time and tide wait for no man

Abstract Background: Familial hypobetalipoproteinemia (FHBL) is the most frequent monogenic form of HBL with a dominant mode of inheritance. Heterozygous patients are often asymptomatic, but the genetic mutation causes a defect of exportation of VLDL from the hepatocytes that remain stuck in the liver causing steatosis. In childhood, the diagnosis of FHBL is often underestimated and guidelines are still lacking. The aim of the study is to describe the phenotypic features of a cohort of children and adolescents with a genetic confirmed FHBL attending our pediatric lipid clinic. Methods: This is a monocentric, observational study collecting anamnestic, anthropometric, biochemical and instrumental data (liver ultrasound and elastographic profile) in children and adolescents with a genetic confirmation of heterozygous FHBL. Results: 12 children and adolescents (4 females), aged 12.14 ± 1.80 years, were genetically diagnosed with heterozygous FHBL. Overweight and/or obesity were identified in 7/12 cases while failure to thrive was detected in 4/12 cases. Only one patient was fully asymptomatic. In 6/12 patients, steatosis was graded from moderate to severe, mainly when accompanied by overweight and/or obesity (p 0.05). Transient elastography was more elevated in FHBL patients if overweight and/or obese (5.65 ± 0.71 vs. 4.60 ± 0.28, p 0.06). Conclusions: Our data document an unexpectedly wide phenotype of FHBL in childhood and adolescence ranging from no symptoms to growth failure or, on the other side, to obesity. Moreover, we document a frequent precocious hepatic involvement in FHBL children, especially if obese and overweight with a potential rapid evolution in fibrosis.