Hypolipidemia due to Familial Hypobetalipoproteinemia in Adolescents

Background/objective: Individuals with heterozygous familial hypobetalipoproteinemia (h-FHBL) due to loss-of-function mutation in the apolipoprotein B gene are typically asymptomatic with mild liver dysfunction, which is often detected incidentally. About 5% to 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 3 patients with hypobetalipoproteinemia, 2 with confirmed h-FHBL, and 1 with suspected h-FHBL.

Case report: 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-old female, were siblings. Patient 3 was a 12 ⁶/₁₂-year-old female. All had total cholesterol ranging from 61 to 87 mg/dL, low-density lipoprotein cholesterol 10 to 28 mg/dL, and triglycerides 19 to 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 apolipoprotein B 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.

Conclusion: 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.