Table 2.

Genes of Interest in the Differential Diagnosis of Familial Combined Hypolipidemia

GeneDisorderMOIFeatures of Differential Diagnosis
Overlapping w/FCHDistinguishing from FCH
APOB Biallelic APOB-related familial hypobetalipoproteinemia 1AR 2Low plasma levels of LDL cholesterol
  • Assoc w/clinical symptoms (e.g. failure to thrive, steatorrhea)
  • HDL cholesterol levels are lower in FCH. 3
MTTP Abetalipoproteinemia ARLow plasma levels of LDL cholesterolAssoc w/clinical symptoms (e.g. failure to thrive, steatorrhea)
PCSK9 Hypocholesterolemia w/↓ LDL cholesterol 4AD
  • Not assoc w/any clinical symptoms
  • Low plasma levels of LDL cholesterol
Normal levels of plasma HDL cholesterol
SAR1B Chylomicron retention disease ARLow plasma levels of LDL & HDL cholesterol
  • Assoc w/clinical symptoms (e.g. failure to thrive, steatorrhea)
  • Plasma triglycerides are not low.

AD = autosomal dominant; AR = autosomal recessive; FCH = familial combined hypolipidemia; HDL = high-density lipoprotein; LDL = low-density lipoprotein; MOI = mode of inheritance

1.

Individuals with a heterozygous, typically truncating pathogenic variant in APOB are usually asymptomatic with mild liver dysfunction and hepatic steatosis. However, about 5%-10% of individuals with heterozygous APOB-related familial hypobetalipoproteinemia (APOB-FHBL) develop relatively more severe non-alcoholic steatohepatitis requiring medical attention and occasionally progressing to cirrhosis.

2.

APOB-FHBL due to a monoallelic, heterozygous pathogenic variant is inherited in an autosomal dominant fashion.

3.
4.

From: Familial Combined Hypolipidemia

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