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]
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.
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 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. 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 history. VLDL appears to be the most affected lipoproteien fraction in type V and there is 3fold increase in synthesis rate as well as decreased fractional catabolism of VLDL.
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
Type V HPL is associated with diabetes mellitus, alcohol abuse, glycogen storage disease type I, Hyperuricemia, Pancreatitis and xanthomatosis.
Causes
Causes of 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 inovolved environmental factors vary, involvement of heavy dirinking, type 2 Diabetes, hormonal therapy and medications are frequently observed.
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.
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