hypobetalipoproteinaemia

Definition
Hypobetalipoproteinemia (HBL) is defined by very low levels (<5th percentile) of total apoB and/or low-density lipoprotein (LDL) cholesterol in plasma (2)

Apolipoprotein B
ApoB-48 and ApoB-100 produced from same gene
ApoB-48 is produced in enterocytes - constituent of chylomicrons
ApoB-100 is produced in hepatocytes - constituent of VLDL and LDL

Primary - inability to produce chylomicrons in enterocytes
AR
Abetalipoproteinaemia
Chylomicron retention disease
AD
Familial hypobetalipoproteinaemia (FHBL)

Secondary - intestinal fat malabsorption
Chronic pancreatitis
Severe liver disease (eg HCV)
Malnutrition
Hyperthyroidism
Strict veganism

Genetics
Abetalipoproteinaemia
Microsomal triglyceride transfer protein (MTP)
Chylomicron retention disease
SARA2 gene mutations
FHBL (2/3)
(i) premature stop codon specifying mutations of APOB (chromosome 2)
~30%
(ii) ANGPTL3 (chromosome 3p21)

(iii) FHBL linked neither to APOB nor to the chromosome 3p21.
~50%

Presentation
Abetalipoproteinaemia / chylomicron retention disease
FTT, anaemia, acanthocytosis, ataxia (similar to Friedreich’s ataxia), retinitis pigmentosa
Heterozygous FHBL
Largely asymptomatic, Low LDL / ApoB
Express ~25% of normal ApoB-100 levels
May have chronic diarrhoea due to partial fat malabsorption
NAFLD (in those with ApoB mutations only) (1)
Can progress to cirrhosis (3)
Homozygous FHBL
Similar to abetalipoproteinaemia, but generally less severe
Severe fat malabsorption
NAFLD
Fat soluble vitamin deficiencies

Management
Fat malabsorption, when present, is treated by limiting the intake of fats containing longchain fatty acids and substituting medium-chain triglycerides to furnish fat calories. Fat-soluble vitamins may need to be given as well. These are available in injectable forms or as water-soluble emulsions. The fatty liver has to date not been treated, because it is not clear how and whether this needs to be done. More studies are needed (2)
Diet and exercise / weight loss improve LFTs and NAFLD

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