Tangier disease

Jump to: navigation, search

WikiDoc Resources for Tangier disease

Articles

Most recent articles on Tangier disease

Most cited articles on Tangier disease

Review articles on Tangier disease

Articles on Tangier disease in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Tangier disease

Images of Tangier disease

Photos of Tangier disease

Podcasts & MP3s on Tangier disease

Videos on Tangier disease

Evidence Based Medicine

Cochrane Collaboration on Tangier disease

Bandolier on Tangier disease

TRIP on Tangier disease

Clinical Trials

Ongoing Trials on Tangier disease at Clinical Trials.gov

Trial results on Tangier disease

Clinical Trials on Tangier disease at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Tangier disease

NICE Guidance on Tangier disease

NHS PRODIGY Guidance

FDA on Tangier disease

CDC on Tangier disease

Books

Books on Tangier disease

News

Tangier disease in the news

Be alerted to news on Tangier disease

News trends on Tangier disease

Commentary

Blogs on Tangier disease

Definitions

Definitions of Tangier disease

Patient Resources / Community

Patient resources on Tangier disease

Discussion groups on Tangier disease

Patient Handouts on Tangier disease

Directions to Hospitals Treating Tangier disease

Risk calculators and risk factors for Tangier disease

Healthcare Provider Resources

Symptoms of Tangier disease

Causes & Risk Factors for Tangier disease

Diagnostic studies for Tangier disease

Treatment of Tangier disease

Continuing Medical Education (CME)

CME Programs on Tangier disease

International

Tangier disease en Espanol

Tangier disease en Francais

Business

Tangier disease in the Marketplace

Patents on Tangier disease

Experimental / Informatics

List of terms related to Tangier disease

To view Lipoprotein Disorders Main Page Click here
To view Hypolipoproteinemia Main Page Click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2], Twinkle Singh, M.B.B.S. [3] Aravind Kuchkuntla, M.B.B.S[4]

Synonyms and Keywords: analphalipoproteinaemia, high density lipoprotein deficiency-type 1, high density lipoprotein deficiency-Tangier type, A-alphalipoprotein Neuropathy, alpha High Density Lipoprotein Deficiency Disease, Cholesterol thesaurismosis, Tangier Disease Neuropathy, Tangier Hereditary Neuropathy

Overview

Tangier Disease is a rare autosomal recessive disease caused by mutation in the ABCA1 gene on chromosome 9. It is characterized by low or absent High density lipoprotein (HDL) and apolipoprotein A1. The mutation affects the efflux of cholesterol from the cells via the ABCA transporter leading to the accumulation of cholesterol esters in the tonsils, peripheral nerves, liver, skin and corneas. Patients typically present with yellow-orange tonsillar enlargement, peripheral neuropathy and corneal opacity. Low HDL is an independent cardiovascular risk factor, therefore these patients are at an increased risk of developing premature coronary artery disease.

Historical Perspective

Classification

Homozygous Heterozygous
Presentation Symptomatic Asymptomatic
Lipid Profile
  • HDL < 5% of normal
  • Apo A1 < 1% of normal
  • LDL < 40% of normal
Pathophysiology Increased fractional catabolism of HDL and Apo A1 Enhanced clearance of HDL and Apo A1
2D Electrophoresis Only preβ-1 HDL present
CVD Risk Variable and related to non-HDL C and splenomegaly Not at higher risk when compared to non-carriers.[9]

Pathophysiology

Pathogenesis

Reverse cholesterol transport

The following algorithm describes the HDL C formation and recycling:[14]

 
 
 
Very small discoidal pre beta-1 HDL picks up free cholesterol from cells via ABCA1 transporter to become small discoidal alpha-4 HDL, this intitial step is disrupted in Tangier disease causing to have only pre beta HDL on 2D electrophoresis[15]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discoidal HDL particles are converted to medium spherical α-3 HDL and larger particles by the esterification of free cholesterol via the enzyme lecithin cholesterol acyltransferase (LCAT) and the addition of Apo A II
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
These particles are further converted to large and very large spherical α-2 and α-1 HDL by the actions of cholesteryl ester transfer protein (CETP). CETP transfers cholesteryl ester from HDL to triglyceride-rich lipoproteins in exchange for triglyceride
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Very large α-1 HDL particles are preferential donors of cholesterol to the liver, and the constituents of these particles can recycle back to form very small discoidal particles and can re-enter the HDL cycle, or be catabolized directly by the kidney or liver
 
 
 


Genetics

Microscopic pathology

The characteristic microscopic features in Tangier disease on histopathological examination include:

Associated Conditions

Conditions associated with Tangier disease include:

Differentiating Tangier disease from other diseases with low HDL C

Low HDL Diagnostic Features

Familial LCAT Deficiency Fish Eye Disease Homozygous Tangier Disease Heterozygous Tangier Disease Apo A1 Deficiency
Gene Defect LCAT LCAT ABCA1 ABCA1 Apo A1
Inheritance Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive Autosomal dominant
Pathogenesis Loss of alpha function only

Pre beta-1 HDL fails to picks up free cholesterol from cells due to mutation in ABCA1 transporter.

Similar to homozygous Defective synthesis of Apo A1 resulting in failure of maturation of HDL causing defective reverse cholesterol transport.
Clinical Features Asymptomatic
Lipid Profile
  • HDL < 5% of normal
  • Apo A1 < 1% of normal
  • LDL < 40% of normal
2D Gel Electrophoresis Pre β-1 and α-4 HDL, LDL with β mobility due to Lipoprotien-X Pre β-1and α-4 HDL with normal pre-β LDL Only preβ-1 HDL present
  • Lack of large α-1 and α-2 HDL particles
  • Normal preβ-1 HDL
Lack of Apo A1 containing HDL particles

Epidemiology and Demographics

  • The prevalence of Tangier disease is estimated to be less than 1/1,000,000.[21]
  • Worldwide, Tangier disease has been diagnosed in about 100 patients.[22]

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

The patients with Tangier disease usually present with the following findings:

Laboratory Findings

Tangier disease is diagnosed with characteristic laboratory finding of very low HDL C and Apo A1.

2D Electrophoresis

Molecular Genotype sequencing

Treatment

Medical Therapy

There are no specific treatment measures are available for treatment of Tangier disease. The mainstay of therapy include:

Surgery

No surgical therapies are indicated.

Prevention

Primary Prevention

  • Patients with homozygous Tangier disease are at higher risk of developing cardiovascular disease at a young age, and according to 2013 ACC/AHA guidelines LDL C levels should be maintained below 70mg/dl.
  • Identifying and optimizing modifiable risk factors is advised.

References

  1. Schmitz G, Assmann G, Robenek H, Brennhausen B (1985). "Tangier disease: a disorder of intracellular membrane traffic". Proc Natl Acad Sci U S A. 82 (18): 6305–9. PMC 391042. PMID 2994070.
  2. Rust S, Walter M, Funke H, von Eckardstein A, Cullen P, Kroes HY; et al. (1998). "Assignment of Tangier disease to chromosome 9q31 by a graphical linkage exclusion strategy". Nat Genet. 20 (1): 96–8. doi:10.1038/1770. PMID 9731541.
  3. Remaley AT, Rust S, Rosier M, Knapper C, Naudin L, Broccardo C; et al. (1999). "Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred". Proc Natl Acad Sci U S A. 96 (22): 12685–90. PMC 23050. PMID 10535983.
  4. Langmann T, Klucken J, Reil M, Liebisch G, Luciani MF, Chimini G; et al. (1999). "Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages". Biochem Biophys Res Commun. 257 (1): 29–33. doi:10.1006/bbrc.1999.0406. PMID 10092505.
  5. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M; et al. (1999). "Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency". Nat Genet. 22 (4): 336–45. doi:10.1038/11905. PMID 10431236.
  6. Bodzioch M, Orsó E, Klucken J, Langmann T, Böttcher A, Diederich W; et al. (1999). "The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease". Nat Genet. 22 (4): 347–51. doi:10.1038/11914. PMID 10431237.
  7. Brousseau ME, Schaefer EJ, Dupuis J, Eustace B, Van Eerdewegh P, Goldkamp AL; et al. (2000). "Novel mutations in the gene encoding ATP-binding cassette 1 in four tangier disease kindreds". J Lipid Res. 41 (3): 433–41. PMID 10706591.
  8. Schaefer EJ, Blum CB, Levy RI, Jenkins LL, Alaupovic P, Foster DM; et al. (1978). "Metabolism of high-density lipoprotein apolipoproteins in Tangier disease". N Engl J Med. 299 (17): 905–10. doi:10.1056/NEJM197810262991701. PMID 211412.
  9. Frikke-Schmidt R, Nordestgaard BG, Stene MC, Sethi AA, Remaley AT, Schnohr P; et al. (2008). "Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease". JAMA. 299 (21): 2524–32. doi:10.1001/jama.299.21.2524. PMID 18523221.
  10. Rust S, Rosier M, Funke H, Real J, Amoura Z, Piette JC; et al. (1999). "Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1". Nat Genet. 22 (4): 352–5. doi:10.1038/11921. PMID 10431238.
  11. Wang S, Smith JD (2014). "ABCA1 and nascent HDL biogenesis". Biofactors. 40 (6): 547–54. doi:10.1002/biof.1187. PMC 4294467. PMID 25359426.
  12. 12.0 12.1 Assmann G, Smootz E (1978). "High density lipoprotein infusion and partial plasma exchange in Tangier disease". Eur J Clin Invest. 8 (3): 131–5. PMID 211037.
  13. Emmerich J, Vergès B, Tauveron I, Rader D, Santamarina-Fojo S, Shaefer J; et al. (1993). "Familial HDL deficiency due to marked hypercatabolism of normal apoA-I". Arterioscler Thromb. 13 (9): 1299–306. PMID 8364014.
  14. Asztalos BF, Tani M, Schaefer EJ (2011). "Metabolic and functional relevance of HDL subspecies". Curr Opin Lipidol. 22 (3): 176–85. doi:10.1097/MOL.0b013e3283468061. PMID 21537175.
  15. Favari E, Calabresi L, Adorni MP, Jessup W, Simonelli S, Franceschini G; et al. (2009). "Small discoidal pre-beta1 HDL particles are efficient acceptors of cell cholesterol via ABCA1 and ABCG1". Biochemistry. 48 (46): 11067–74. doi:10.1021/bi901564g. PMID 19839639.
  16. Ferrans VJ, Fredrickson DS (1975). "The pathology of Tangier disease. A light and electron microscopic study". Am J Pathol. 78 (1): 101–58. PMC 1915033. PMID 162820.
  17. Reinhart WH, Gössi U, Bütikofer P, Ott P, Sigrist H, Schatzmann HJ; et al. (1989). "Haemolytic anaemia in analpha-lipoproteinaemia (Tangier disease): morphological, biochemical, and biophysical properties of the red blood cell". Br J Haematol. 72 (2): 272–7. PMID 2757970.
  18. Koseki M, Matsuyama A, Nakatani K, Inagaki M, Nakaoka H, Kawase R; et al. (2009). "Impaired insulin secretion in four Tangier disease patients with ABCA1 mutations". J Atheroscler Thromb. 16 (3): 292–6. PMID 19556721.
  19. Sampietro T, Puntoni M, Bigazzi F, Pennato B, Sbrana F, Dal Pino B; et al. (2009). "Images in cardiovascular medicine. Tangier disease in severely progressive coronary and peripheral artery disease". Circulation. 119 (20): 2741–2. doi:10.1161/CIRCULATIONAHA.108.812164. PMID 19470903.
  20. Hooper AJ, Robertson K, Ng L, Kattampallil JS, Latchem D, Willsher PC; et al. (2009). "A novel ABCA1 nonsense mutation, R1270X, in Tangier disease associated with an unrecognised bleeding tendency". Clin Chim Acta. 409 (1–2): 136–9. doi:10.1016/j.cca.2009.08.017. PMID 19723515.
  21. "Orphanet: Tangier disease".
  22. Puntoni M, Sbrana F, Bigazzi F, Sampietro T (2012). "Tangier disease: epidemiology, pathophysiology, and management". Am J Cardiovasc Drugs. 12 (5): 303–11. doi:10.2165/11634140-000000000-00000. PMID 22913675.
  23. 23.0 23.1 23.2 Schaefer EJ, Anthanont P, Diffenderfer MR, Polisecki E, Asztalos BF (2016). "Diagnosis and treatment of high density lipoprotein deficiency". Prog Cardiovasc Dis. 59 (2): 97–106. doi:10.1016/j.pcad.2016.08.006. PMID 27565770.
  24. Iatan I, Alrasadi K, Ruel I, Alwaili K, Genest J (2008). "Effect of ABCA1 mutations on risk for myocardial infarction". Curr Atheroscler Rep. 10 (5): 413–26. PMID 18706283.
  25. Gibbels, E.; Schaefer, HE.; Runne, U.; Schröder, JM.; Haupt, WF.; Assmann, G. (1985). "Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy. Clinical, biochemical, electrophysiological, and morphological evaluation, including electron microscopy of nerve, muscle, and skin biopsies". J Neurol. 232 (5): 283–94. PMID 2997405.
  26. Pietrini, V.; Rizzuto, N.; Vergani, C.; Zen, F.; Ferro Milone, F. (1985). "Neuropathy in Tangier disease: A clinicopathologic study and a review of the literature". Acta Neurol Scand. 72 (5): 495–505. PMID 4082916. Unknown parameter |month= ignored (help)
  27. Gibbels E, Schaefer HE, Runne U, Schröder JM, Haupt WF, Assmann G (1985). "Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy. Clinical, biochemical, electrophysiological, and morphological evaluation, including electron microscopy of nerve, muscle, and skin biopsies". J Neurol. 232 (5): 283–94. PMID 2997405.
  28. Pietrini V, Rizzuto N, Vergani C, Zen F, Ferro Milone F (1985). "Neuropathy in Tangier disease: A clinicopathologic study and a review of the literature". Acta Neurol Scand. 72 (5): 495–505. PMID 4082916.
  29. Chung S, Timmins JM, Duong M, Degirolamo C, Rong S, Sawyer JK; et al. (2010). "Targeted deletion of hepatocyte ABCA1 leads to very low density lipoprotein triglyceride overproduction and low density lipoprotein hypercatabolism". J Biol Chem. 285 (16): 12197–209. doi:10.1074/jbc.M109.096933. PMC 2852959. PMID 20178985.
  30. Huang Y, von Eckardstein A, Wu S, Langer C, Assmann G (1995). "Generation of pre-beta 1-HDL and conversion into alpha-HDL. Evidence for disturbed HDL conversion in Tangier disease". Arterioscler Thromb Vasc Biol. 15 (10): 1746–54. PMID 7583552.



Linked-in.jpg