Version June 2024
| Disease | Genetic mutation/ inheritance | Functional significance | Prevalence | Laboratory features | LDL-C level | Sequelae | Treatment |
| Abetalipoproteinemia | Mutation in the microsomal transfer protein, autosomal recessive inheritance | Microsomal transfer protein is responsible for the intracellular assembly of apoB and lipids in the liver and intestine | <1 in 1,000,000 | Absent LDL and VLDL (no apoB-containing lipoproteins), triglycerides <30 mg/dL | Not detectable to 20 mg/dL[1] HDL-C 30 mg/dL[1] | Steatorrhea in infancy, failure to thrive, acanthosis, retinitis pigmentosa | Fat soluble vitamin supplementation (A, D, E, K) |
| Chylomicron retention disease (Anderson disease) | Autosomal recessive mutation of Sar1b | Sar1b mutation disrupts protein transport from the endoplasmic reticulum to the Golgi in enterocytes | 1 in 20,000 to 25,000 births | Low LDL-C and HDL-C, elevated creatinine kinase Absence of chylomicrons and apoB-48 post-prandially | 27 mg/dL ± 15 mg/dL HDL-C 18 ± 3 mg/dL[2] | Infancy with failure to thrive and steatorrhea, abdominal distension, and vomiting. Deficiency of vitamin E and other fat-soluble vitamins, which may have neurological consequences (eg, retinopathy, hypo- or areflexia, myopathy), hepatic steatosis. | Removal of long chain fatty acids from the diet, nutritional support, and supplements of fat-soluble vitamins |
| Homozygous familial hypobetalipoproteinemia | Autosomal recessive inheritance of APOB truncation variant (this results from insertion of a premature stop codon) | Interference with the full-length translation of the apoB molecule. This causes a truncated apoB molecule.* Shorter truncations of apoB, which interfere more severely with hepatic secretion of both VLDL-containing mutant apoB and apoB-100. | Absent to low LDL, depending on how short the truncated gene is. Low to absent triglycerides, low HDL[3]. | Not detectable | With short truncations of apoB-impaired chylomicron secretion and steatorrhea at birth. In milder forms, acanthosis may be seen but nothing else. | ||
| Heterozygous familial hypobetalipoproteinemia | Mutation of APOB results from insertion of a premature stop codon | Interference with the full-length translation of the apoB molecule. This causes a truncated apoB molecule. | 1 in 10,000 | Low LDL-C | 21 ± 6 (mg/dL)[4] | Protective for ASCVD; nonalcoholic fatty liver disease is present in an unknown percentage of individuals | Monitor for nonalcoholic fatty liver disease |
| Loss-of-function mutations of PCSK9 | Various mutations in PCSK9 gene | Decreased degradation of the LDL receptor | 2 to 3% | LDL-C is 15 to 28% reduced in heterozygotes. Lower LDL-C seen in compound heterozygotes. | Heterozygotes 110 mg/dL[5] Homozygotes 15 mg/dL[5] | Reduced ASCVD risk | |
| Familial combined hypolipidemia | Loss-of-function mutations in angiopoietin-like protein 3 | Increased activity of lipoprotein lipase and endothelial lipase (enzymes that break down triglycerides) | Not reported¶ | Reduced levels of all plasma lipoproteins except lipoprotein(a) | 19 to 54 mg/dL | Heterozygotes; no fatty liver disease. Homozygotes; no diabetes or ASCVD. | |
| Variant ASGR1 | Loss-of-function variants of a subunit of the ASGR1, heterozygous | The hepatic carbohydrate-recognizing ASGR1 mediates the endocytosis/lysosomal degradation of desialylated glycoproteins following binding to terminal galactose/N-acetylgalactosamine | Not reported | Non-HDL-C (in most persons this is LDL-C) is 15 mg/dL lower than in persons without genetic variant | 92 (wide range, IQR 19-170)[6] | Protective for ASCVD |
LDL: low-density lipoprotein; VLDL: very low-density lipoprotein; apoB: apolipoprotein b; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; ASCVD: atherosclerotic cardiovascular disease; ASGR1: asialoglycoprotein receptor.
* Adopting similar terminology to that used for apoB-100 (normally produced in the liver) and apoB-48 (normally produced by the gut), a wide range of apoB variants have been described to be associated with low-circulating LDL-C, ranging from apoB2 to apoB 89.1. Truncated apoB 27.6 or less is undetectable in the circulation.
¶ 20% of loss with abetalipoproteinemia.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
