Hypolipidemia due to familial hypobetalipoproteinemia in adolescents

Background/Objective Individuals with heterozygous familial hypobetalipoproteinemia (h-FHBL) due to loss of function mutation in the APOB gene are typically asymptomatic with mild liver dysfunction, which is often detected incidentally. About 5-10% of those with h-FHBL develop steatohepatitis which occasionally progress to cirrhosis especially in the presence of alcohol use, excess calorie consumption, or liver injury. We report three patients with hypobetalipoproteinemia, two with confirmed h-FHBL and one with suspected h-FHBL. Case reports Three asymptomatic adolescents presented with low lipid levels detected on screening laboratory studies. Patient 1, a 13 6/12-year-old male and patient 2, a 15 9/12-year female, were siblings. Patient 3 was a 12 6/12-year-old female. All had total cholesterol ranging from 61-87 mg/dl, low density lipoprotein cholesterol 10-28 mg/dl, and triglycerides 19-36 mg/dl. Aspartate transaminase and alanine transaminase levels were normal in patients 1 and 3 and were elevated in patient 2. Liver ultrasounds of patients 2 and 3 showed hepatic steatosis. Molecular testing identified pathogenic variant of APOB gene in patients 1 and 2, c.133C>T(p.Arg.45Ter) confirming the diagnosis of h-FHBL. Discussion More studies are needed in children with h-FHBL and other forms of hypobetalipoproteinemia to improve awareness of these disorders and to develop guidelines for monitoring and risk reduction in affected patients. Conclusions Health care providers should be aware that persistent hypolipidemia may indicate h-FHBL, which can be a risk factor for liver dysfunction. Youth with h-FHBL should be counseled about lifestyle modifications and screened for the development of metabolic dysfunction-associated steatotic liver disease.