Familial hyperchylomicronemia: Difference between revisions
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==Laboratory finding== | ==Laboratory finding== | ||
==Treatment== | ==Treatment== | ||
The main therapeutical approach of Type I hyperlipoproteinemia is based on diet treatment to reduce triglyceride (TG) levels.20 TG-lowering drugs, such as niacin and fibrates, are not effective in patients with type I hyperlipoproteinemia.21 Orlistat, a gastric lipase inhibitor that reduces fat availability, has been used successfully in the treatment of moderate and severe LPL deficiency.22 and 23 Recently, gene replacement using alipogene tiparvovec has been the very first therapy approved by European Medicines Agency for the treatment of type I hyperlipoproteinemia.24 Alipogene tiparvovec introduces a human LPL gene into the body, resulting in the production of functional LPL. 25 However, this gene therapy is indicated only in adults with genetic diagnosis of LPL deficiency who have had recurrent pancreatitis and with a residual lipoprotein mass in the circulation. 24 and 26 Thus, careful genetic screening and functional testing of LPL are required to identify patients eligible for this new therapeutic approach. | |||
==Prevention== | ==Prevention== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Revision as of 13:33, 4 November 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Vishal Devarkonda, M.B.B.S[2]
Synonyms and keywords: Type I hyperlipoproteinemia, Burger-Grutz syndrome, primary hyperlipoproteinemia, lipoprotein lipase deficiency, LPL deficiency, idiopathic hyperlipemia, essential hyperlipemia, familial hyperlipemia, lipase D deficiency, hyperlipoproteinemia type IA, familial chylomicronemia, familial lipoprotein lipase deficiency, and familial hyperchylomicronemia.
Overview
This very rare form is due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicron which are the particles that transfer fatty acids from the digestive tract to the liver. Lipoprotein lipase is also responsible for the initial breakdown of endogenously made triacylglycerides in the form of very low density lipoprotein (VLDL). As such, one would expect a defect in LPL to also result in elevated VLDL. Its prevalence is 0.1% of the population.
Classification
Type 1A
It occurs due to deficiency of lipoprotein lipase enzyme.
Type 1B
Altered apolipoprotein C2 causes type 1B hyperlipoproteinemia
Type 1C
Presence of LPL inhibitor is the cause of type 1C hyperlipoproteinemia
Historical Perspective
Pathophysiology
- Type I hyperlipoproteinemia is a rare autosomal recessive disorder of lipoprotein metabolism. [1][2][3]
Pathogenesis
- Lipoprotein lipase(LPL) hydrolysis Triglyceride-rich lipoproteins (TG) such as chylomicrons and very low-density lipoproteins. It catalyzes, the removal of TG from bloodstream generating free fatty acids for tissues.
- For full enzymatic activity, LPL requires following cofactors:-
- Apolipoprotein C-II and apolipoprotein A-V that are LPL activators
- Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein
- Lipase maturation factor 1
- Development of Type I hyperlipoproteinemia is the result of functional mutations in one of all these genes result in type I hyperlipoproteinemia.
Familial lipoprotein lipase inhibitor
- Familial lipoprotein lipase inhibitor seems to be inherited as an autosomal dominant trait.
- Postheparin plasma LPL activity is decreased, adipose tissue LPL activity is elevated, and plasma levels of functional apoC-I1 are normal.
- Functionally inactive or absent lipoprotein lipase emzyme, results in massive accumulation of chylomicrons, with extremely high level of plasma triglycerides.
Causes
Differential diagnosis
Epidemiology and Demographics
Familial hyperchylomicronemia, is a rare autosomal recessive disorder of lipoprotein metabolism estimated to affect approximately one per million individuals. In some ethnic groups, the frequency of this disorder is several fold higher (i.e., French Canadians, Afrikaner).
Risk Factors
Diagnosis
History/symptoms
The signs and symptoms of hyperlipoproteinemia type 1 usually begin during childhood. Approximately 25 percent of affected individuals develop symptoms before age 1. The characteristic features of hyperlipoproteinemia type 1 include: Abdominal pain (may manifest as colic in infancy) Nausea, vomiting, loss of appetite Failure to thrive in infancy Musculoskeletal pain (pain in the muscles and bones) Xanthomas (small, yellow, fat deposits in the skin) Pancreatitis Enlarged liver and spleen
Physical examination
Laboratory finding
Treatment
The main therapeutical approach of Type I hyperlipoproteinemia is based on diet treatment to reduce triglyceride (TG) levels.20 TG-lowering drugs, such as niacin and fibrates, are not effective in patients with type I hyperlipoproteinemia.21 Orlistat, a gastric lipase inhibitor that reduces fat availability, has been used successfully in the treatment of moderate and severe LPL deficiency.22 and 23 Recently, gene replacement using alipogene tiparvovec has been the very first therapy approved by European Medicines Agency for the treatment of type I hyperlipoproteinemia.24 Alipogene tiparvovec introduces a human LPL gene into the body, resulting in the production of functional LPL. 25 However, this gene therapy is indicated only in adults with genetic diagnosis of LPL deficiency who have had recurrent pancreatitis and with a residual lipoprotein mass in the circulation. 24 and 26 Thus, careful genetic screening and functional testing of LPL are required to identify patients eligible for this new therapeutic approach.
Prevention
- ↑ Pingitore P, Lepore SM, Pirazzi C, Mancina RM, Motta BM, Valenti L; et al. (2016). "Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia". J Clin Lipidol. 10 (4): 816–23. doi:10.1016/j.jacl.2016.02.015. PMID 27578112.
- ↑ Young SG, Zechner R (2013). "Biochemistry and pathophysiology of intravascular and intracellular lipolysis". Genes Dev. 27 (5): 459–84. doi:10.1101/gad.209296.112. PMC 3605461. PMID 23475957.
- ↑ Pasalić D, Jurcić Z, Stipancić G, Ferencak G, Leren TP, Djurovic S; et al. (2004). "Missense mutation W86R in exon 3 of the lipoprotein lipase gene in a boy with chylomicronemia". Clin Chim Acta. 343 (1–2): 179–84. doi:10.1016/j.cccn.2004.01.029. PMID 15115692.