Case report of familial hypobetalipoproteinemia: a novel APOB mutation and literature review

Familial hypobetalipoproteinemia an autosomal dominantly inherited disorder of lipid metabolism characterized by a <5th percentile plasma levels of low-density lipoprotein cholesterol or total apolipoprotein B, caused by mutations in the APOB gene. Patients with heterozygous APOB-related familial hypobetalipoproteinemia are often diagnosed incidentally because they are usually asymptomatic or manifest with mild liver dysfunction.These patients may need genetic testing or follow-up tests on lipid profile and liver function.To the editor, Familial hypobetalipoproteinemia (FHBL) is an autosomal codominant inherited disorder of lipid metabolism characterized by a plasma level of apolipoprotein B (ApoB) below the 5th percentile.Low-density lipoprotein (LDL) cholesterol levels are usually between 20-50 mg/ dL.The known causative genes for FHBL that have been discovered to date include APOB and PCSK9. 1,2)In this report, we present a case of a novel mutation in the APOB gene identified in a Korean boy with low LDL cholesterol level and nonalcoholic fatty liver disease (NAFLD).A 14-year-old Korean boy was referred to our clinic due to incidentally identified low LDL cholesterol and elevated aminotransferase.He complained of no specific symptoms or signs associated with hypocholesterolemia, including growth retardation, steatorrhea, or neurologic dysfunction.When he presented to the clinic, his height, weight, body mass index, and waist circumference were 164 cm (-0.14 standard deviation score [SDS]), 56.9 kg (0.09 SDS), 21.15 kg/m 2 (0.13 SDS), and 70 cm (-0.27SDS), respectively.No hepatomegaly was observed.Initial laboratory tests showed low LDL cholesterol and ApoB and elevated aminotransferase levels (Table 1).Abdominal computed tomography revealed severe fatty liver and hepatosplenomegaly (Fig. 1).Tests for exclusion of other causes of fatty liver were conducted.Tests for hepatitis A, B, and C were negative, and serum antibodies related to autoimmune hepatitis were negative.Levels of alpha-1-antitrypsin and ceruloplasmin were within the normal ranges.Oral vitamin D supplement was started (25,000 IU/mo) for vitamin D insufficiency.He performed aerobic exercise and maintained a diet (high in fruits, vegetables, protein, and whole grains and low in saturated fats, simple sugars, and salt) for treatment of NAFLD.Five months later, his height, weight, and body mass index were 167 cm (-0.01 SDS), 57.4 kg (-0.05 SDS), and 20.58 kg/m 2 (-0.13 SDS), respectively.Laboratory tests (Table 1) revealed continued low LDL cholesterol and ApoB levels, but his aminotransferase level was within the normal range.A multigene panel test associated with hereditary dyslipidemia was conducted.A novel heterozygous mutation for p.Lys3846Ter (c.11536A>T) was identified in the APOB gene (http://www.hgmd.cf.ac.uk, access date: July 20th, 2022).The variant was absent in control subjects according to gnomAD and the Korean Reference Genome Database.The same mutation was not detected in his parents, who both showed normal ApoB levels.The variant was classified as likely pathogenic according to American College of Medical Genetics guidelines.