Hyperlipoproteinemia type 5
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ;Associate Editor(s)-in-Chief: Shivani Chaparala M.B.B.S [2] Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [3]
Synonyms and keywords: : Hyperchylomicronemia,Late-Onset, Hyperchylomicronemia With Hyperprebetalipoproteinemia, Familial, Mixed Hyperlipidemia, Type V Hyperlipemia, Hyperlipidemia Type V, Type 5 Hyperlipoproteinemia, Type 5 Hyperlipemia, Type 5 HPL, Type V HPL, Combined Fat And Carbohydrate Induced Hyperlipidemia, Mixed Hypertriglyceridemia, Endogenous Hypertriglyceridemia.
For the main page about other hyperlipoproteinemias click here.
For the main page on all lipoprotein disorders click here.
Overview
Type 5 Hyperlipoproteinemia (HLP) is a severe type of hyperlipidemia, characterized by an increase in both very-low-density lipoproteins (VLDLs) and chylomicrons in the plasma of fasting subjects on a regular diet. The metabolic defects responsible for type 5 HLP have been a matter of dispute.Although some patients seem to have "primary" type 5 HLP, this phenotype is often associated with secondary factors, eg, diabetes, obesity, alcoholism, nephrotic syndrome, or hypo- thyroidism. Primary type 5 HLP usually appears first in adulthood, a characteristic that distinguishes it from familial deficiency of lipoprotein lipase (type 1 HLP), which is present from birth. Type 5 HLP has been postulated to be the result of a defective clearance of triglycéride (TG)-rich lipoproteins,although lipoprotein lipase is not absent. Another suggested mechanism is of VLDL TG's overproduction.This abnormality could cause an increase in both VLDL and chylomicrons because these two lipoproteins compete with each other for clearance from plasma; in other words, excess production of VLDL alone theoretically could saturate the lipolytic system for plasma TGs and thereby interfere with removal of chylomicrons. It is a more complicated form of type I and more closely related with acquired environmental factors but no association with reduced Lipoprotein lipase or apolipoprotein C-II activity as in type I.
Pathophysiology
The two main sources of plasma triglycerides (also known as triacylglycerol) are exogenous (i.e., from dietary fat) and carried in chylomicrons, and endogenous (from the liver) and carried in very-low-density lipoprotein (VLDL) particles. In capillaries within fat and muscle tissue, these lipoproteins and chylomicrons are hydrolyzed by lipoprotein lipase into free fatty acids. After a meal, over 90% of the circulating triglycerides originate in the intestine and are secreted in chylomicrons, whereas during periods of fasting, endogenous triglycerides secreted by the liver as VLDL predominate. The increase in plasma of triglyceride-rich lipoproteins results from increased production from the liver and intestine (by means of upregulated synthetic and secretory pathways) or through decreased peripheral catabolism (mainly from reduced lipoprotein lipase activity). VLDL appears to be the most affected lipoprotein fraction in type V and there is 3fold increase in synthesis rate as well as decreased fractional catabolism of VLDL.Mutations in the APOA5 gene, leading to truncated apolipoprotein A-V devoid of lipid-binding domains located in the carboxy-terminal end of the protein, if present in the homozygous state, are expected to cause severe type V hyperlipidemia in patients with no mutations in LPL or APOC2 genes. If present in the heterozygous state, these mutations predispose to hypertriglyceridemia in combination with other genetic factors or pathological conditions.The absence of manifestations until middle age, suggest that the cause of type V hyperlipoproteinemia(HLP) is multifactorial including a combination of environmental, hormonal and genetic factors. In patients with type V HLP, the presence of underlying diseases or contributing factors such as Diabetes and alcohol abuse is confirm in 2/3rd of patients and the remaining patients usually show type IV HLP and have hypertriglyceridemia in the family.
Genetics
Precise genetic patterns have not been determined for type V HLP and it has been suggested that type V may be due to number of genetic defects. Among them, the apo E and its isoforms may have an important clinical significance in type V HLP and may affect the catabolism of triglyceride rich lipoproteins. The presence of apo E4 allele may be the genetic factor that predisposes to the development of type V due to delayed lipoprotein clearance.
Associated Conditions
- diabetes mellitus
- alcohol abuse
- glycogen storage disease type I
- Hyperuricemia
- Pancreatitis
- xanthomatosis.
Causes
Type V hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. It rarely shows familial occurrence, but its inheritance is variable. Therefore, type V HLP is usually considered to be triggered by acquired environmental factors in individuals with some congenital susceptibility to altered triglyceride metabolism (genetic factors). While the involved environmental factors vary, involvement of heavy drinking, type 2 Diabetes, hormonal therapy and medications are frequently observed.[1]
Causes by Pathophysiology
| Congenital (Genetic) Factors | Acquired (Environmental) Factors |
|---|---|
|
Epidemiology and Demographics
- Average triglyceride levels in type V hyperlipoproteinemia are lower for women than for men before age 50.
- In Western population, LPL gene abnormalities were observed in 10% of patients with type V HLP.
Risk Factors
- Family history of dyslipoproteinemia
- Diabetes
- Alcohol abuse
- Obesity
Natural History, Complications and Prognosis
Complications
Diagnosis
Diagnostic Criteria
- I. Demonstration of an increase in VLDL in addition to hyperchylomicronemia.
- II. The absence of LPL deficiency, Apolipoprotein C-II deficiency, Apo E deficiency.
Definitely diagnosed if both I and II are fulfilled.
- Fasting chylomicronemia can be diagnosed by confirming the presence of chylomicrons and excess VLDL on agarose gel electrophoresis or ultracentrifugal analysis. A simple technique is to refrigerate plasma overnight and examine the specimen for a creamy supernatant from chylomicrons and a turbid VLDL-rich infranatant.This latter finding of a turbid infranatant is not seen in patients with type I hyperlipoproteinemia, in which only chylomicrons accumulate and the infranatant is clear.
Differentiating HLP type 5 from other Hyperlipoproteinemia's
- HLP type 5 must be differentiated from other diseases that cause abnormal increase in lipids in the blood.
- Familial hyperchylomicronemia
- Familial hypercholesterolemia/familial combined hyperlipidemia
- Dysbetalipoprotenemia
- Primary Hypertriglyceridemia/Primary Hypertriglyceridemia
Symptoms =
- Recurrent abdominal pain
- Eruptive xanthomas
Laboratory Findings
Treatment
Pharmacotherapy
- Lipid lowering drugs
NOTE:Caution against possible exacerbation of glucose tolerance is necessary in the treatment of Diabetic patients with Nicotinic acid.
Secondary Prevention
- Strict restriction of fat intake
- Elimination of acquired environmental factors
- Weight reduction
References
- ↑ Diagnosis and Management of Type I and Type V Hyperlipoproteinemia Takanari Gotoda1), Koji Shirai2), Takao Ohta3), Junji Kobayashi4), Shinji Yokoyama5) 17), Shinichi Oikawa6), Hideaki Bujo7), Shun Ishibashi8), Hidenori Arai9), Shizuya Yamashita10), Mariko Harada-Shiba11), Masaaki Eto12), Toshio Hayashi13), Hirohito Sone14), Hiroaki Suzuki15), Nobuhiro Yamada