Heterozygous Familial Hypobetalipoproteinemia: description of phenotype in affected children and adolescents in the Era of Obesityd

Patrizia Bruzzi; Giulia Cammarata; Di Biase Anna Rita; Antonio Colecchia; Lorenzo Iughetti

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ESPE Abstracts (2024) 98 P1-150

ESPE2024 Poster Category 1 Fat, Metabolism and Obesity 3 (10 abstracts)

Heterozygous Familial Hypobetalipoproteinemia: description of phenotype in affected children and adolescents in the Era of Obesity.

Patrizia Bruzzi ¹ , Giulia Cammarata ² , Anna Rita Di Biase ¹ , Antonio Colecchia ³ & Lorenzo Iughetti ⁴

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¹Pediatric Unit, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy. ²Post-graduate School of Pediatrics, Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy. ³Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy. ⁴Pediatric Unit, Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy

Background: Hypobetalipoproteinemias (HBL) is a heterogeneous group of disorders characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (ApoB). Familial hypobetalipoproteinemia (FHBL) is the most frequent monogenic form of HBL with a dominant mode of inheritance. It may be due to loss-of-function mutations in APOB or, less frequently, in other genes. 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 firstly steatosis and/or steatohepatitis and then, fibrosis and cirrhosis. In childhood, the diagnosis of FHBL is often underestimated and guidelines are still lacking.

Aims: 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 (lipid and glucose profile, liver function) and instrumental (liver ultrasound and elastographic profile) data in children and adolescents with a genetically confirmation of heterozygous FHBL.

Results: 12 children and adolescence (4 females), aged 12.14 ± 1.80 years, were genetically diagnosed with heterozygous FHBL (9/12 carrying a mutation on ApoB gene, 2/12 on ANGPTL8 gene and one case with a mutation on MYLIP gene). At diagnosis, overweight and/or obesity were identified in 7/12 cases. Only one patient was fully asymptomatic. In all cases, lipid assessment was suggestive of FHBL (mean TC 80.41 ± 14.81 and LDL-C 31.54 ± 12.88 mg/dl) independently from BMI SDS (obese vs. normal-weight patients: p 0.62 and 0.39, respectively). In 6/12 patients, steatosis was graded from moderate to severe, mainly when accompanied by overweight and/or obesity (p 0.05). Moreover, transient elastography, an indirect surrogate of fibrosis, was more elevated in FHBL patients if overweight and/or obese (5.65 ± 0.71 vs. 4.60 ± 0.28, p 0.06).

Conclusion: Our data document an unexpectedly wide phenotype of FHBL in childhood and adolescence with a high percentage of overweight or obesity. Moreover, we document a frequent precocious hepatic involvement in FHBL children, especially if obese and overweight, with a potential rapid evolution in fibrosis. In conclusion, even if these preliminary data require the confirmation from sizable cohort, they support the need of a precocious diagnosis of FHBL in childhood that could let to early plan a personalized follow up. Overweight or obesity seem to be concurrent risk factors for a rapid progression of liver damage.