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Tangier disease(TGD)

MedGen UID:
52644
Concept ID:
C0039292
Disease or Syndrome
Synonyms: A-alphalipoprotein neuropathy; Alpha high density lipoprotein deficiency disease; Analphalipo-proteinemia; Cholesterol thesaurismosis; Familial high density lipoprotein deficiency disease; Familial Hypoalphalipo-proteinemia; Hdl lipoprotein deficiency disease; High density lipoprotein deficiency, Tangier type; High density lipoprotein deficiency, type 1; TGD
SNOMED CT: Cholesterol thesaurismosis (15346004); Analphalipoproteinemia (15346004); Tangier disease (723579009); Defective adenosine triphosphate-binding cassette transporter A1 (723579009); Analphaliproteinemia (15346004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ABCA1 (9q31.1)
 
Monarch Initiative: MONDO:0008783
OMIM®: 205400
Orphanet: ORPHA31150

Disease characteristics

Excerpted from the GeneReview: Tangier Disease
Tangier disease is characterized by severe deficiency or absence of high-density lipoprotein (HDL) in the circulation resulting in tissue accumulation of cholesteryl esters throughout the body, particularly in the reticuloendothelial system. The major clinical signs of Tangier disease include hyperplastic yellow-orange tonsils, hepatosplenomegaly, and peripheral neuropathy, which may be either relapsing-remitting or chronic progressive in nature. Rarer complications may include corneal opacities that typically do not affect vision, premature atherosclerotic coronary artery disease occurring in the sixth and seventh decades of life (not usually before age 40 years), and mild hematologic manifestations, such as mild thrombocytopenia, reticulocytosis, stomatocytosis, or hemolytic anemia. The clinical expression of Tangier disease is variable, with some affected individuals only showing biochemical perturbations. [from GeneReviews]
Authors:
John R Burnett  |  Amanda J Hooper  |  Sally PA McCormick, et. al.   view full author information

Additional descriptions

From OMIM
Tangier disease (TGD) is an autosomal recessive disorder characterized by markedly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters. Clinical features include very large, yellow-orange tonsils, enlarged liver, spleen and lymph nodes, hypocholesterolemia, and abnormal chylomicron remnants (Brooks-Wilson et al., 1999).  http://www.omim.org/entry/205400
From MedlinePlus Genetics
Tangier disease is an inherited disorder characterized by significantly reduced levels of high-density lipoprotein (HDL) in the blood. HDL transports cholesterol and certain fats called phospholipids from the body's tissues to the liver, where they are removed from the blood. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. Because people with Tangier disease have very low levels of HDL, they have a moderately increased risk of cardiovascular disease.

Additional signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood (mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-colored tonsils. Affected individuals often develop atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of the outermost layer of the eye (corneal clouding), and type 2 diabetes.  https://medlineplus.gov/genetics/condition/tangier-disease

Clinical features

From HPO
Atherosclerosis
MedGen UID:
13948
Concept ID:
C0004153
Disease or Syndrome
A condition characterized by patchy atheromas or atherosclerotic plaques which develop in the walls of medium-sized and large arteries and can lead to arterial stenosis with reduced or blocked blood flow.
Coronary artery atherosclerosis
MedGen UID:
3623
Concept ID:
C0010054
Disease or Syndrome
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries, which increases the risk of myocardial ischemia.
Myocardial infarction
MedGen UID:
10150
Concept ID:
C0027051
Disease or Syndrome
Necrosis of the myocardium caused by an obstruction of the blood supply to the heart and often associated with chest pain, shortness of breath, palpitations, and anxiety as well as characteristic EKG findings and elevation of serum markers including creatine kinase-MB fraction and troponin.
Left ventricular hypertrophy
MedGen UID:
57442
Concept ID:
C0149721
Disease or Syndrome
Enlargement or increased size of the heart left ventricle.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Peripheral demyelination
MedGen UID:
451074
Concept ID:
C0878575
Pathologic Function
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Impaired pain sensation
MedGen UID:
373348
Concept ID:
C1837522
Finding
Reduced ability to perceive painful stimuli.
Impaired temperature sensation
MedGen UID:
866867
Concept ID:
C4021222
Finding
A reduced ability to discriminate between different temperatures.
Facial diplegia
MedGen UID:
322796
Concept ID:
C1836003
Finding
Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy).
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Decreased HDL cholesterol concentration
MedGen UID:
57731
Concept ID:
C0151691
Finding
An decreased concentration of high-density lipoprotein cholesterol in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Decreased circulating apolipoprotein A-I concentration
MedGen UID:
1634454
Concept ID:
C4703545
Finding
Concentration of apolipoprotein A-I below the lower limit of normal. Apolipoprotein A-I is the major protein component of high density lipoprotein (HDL) in plasma. Defects in this gene are associated with HDL deficiencies, including Tangier disease.
Elevated circulating apolipoprotein A-II concentration
MedGen UID:
1638249
Concept ID:
C4703546
Finding
An increased concentration in blood of apolipoprotein A-II, a major component of HDL particles, associated with triglyceride and glucose metabolism.
Ectropion
MedGen UID:
4448
Concept ID:
C0013592
Disease or Syndrome
An outward turning (eversion) or rotation of the eyelid margin.
Cicatricial ectropion
MedGen UID:
102327
Concept ID:
C0155196
Disease or Syndrome
An outward turning (eversion) or rotation of the eyelid margin (i.e., ectropion) caused by shortening or contraction of the anterior or middle lamellae related to scarring.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Professional guidelines

PubMed

Bonilha I, Luchiari B, Nadruz W, Sposito AC
Arch Endocrinol Metab 2023 Jan 18;67(1):3-18. doi: 10.20945/2359-3997000000585. PMID: 36651718Free PMC Article
Koseki M, Yamashita S, Ogura M, Ishigaki Y, Ono K, Tsukamoto K, Hori M, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Aug 1;28(8):802-810. Epub 2021 May 14 doi: 10.5551/jat.RV17053. PMID: 33994407Free PMC Article
Schaefer EJ, Anthanont P, Diffenderfer MR, Polisecki E, Asztalos BF
Prog Cardiovasc Dis 2016 Sep-Oct;59(2):97-106. Epub 2016 Aug 24 doi: 10.1016/j.pcad.2016.08.006. PMID: 27565770Free PMC Article

Recent clinical studies

Etiology

Koseki M, Yamashita S, Ogura M, Ishigaki Y, Ono K, Tsukamoto K, Hori M, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Aug 1;28(8):802-810. Epub 2021 May 14 doi: 10.5551/jat.RV17053. PMID: 33994407Free PMC Article
Hooper AJ, Hegele RA, Burnett JR
Curr Opin Lipidol 2020 Apr;31(2):80-84. doi: 10.1097/MOL.0000000000000669. PMID: 32022754
Westerterp M, Fotakis P, Ouimet M, Bochem AE, Zhang H, Molusky MM, Wang W, Abramowicz S, la Bastide-van Gemert S, Wang N, Welch CL, Reilly MP, Stroes ES, Moore KJ, Tall AR
Circulation 2018 Aug 28;138(9):898-912. doi: 10.1161/CIRCULATIONAHA.117.032636. PMID: 29588315Free PMC Article
Nair DR, Nair A, Jain A
Curr Pharm Des 2014;20(40):6230-7. doi: 10.2174/1381612820666140620122412. PMID: 24953397
Soumian S, Albrecht C, Davies AH, Gibbs RG
Vasc Med 2005 May;10(2):109-19. doi: 10.1191/1358863x05vm593ra. PMID: 16013195

Diagnosis

Koseki M, Yamashita S, Ogura M, Ishigaki Y, Ono K, Tsukamoto K, Hori M, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Aug 1;28(8):802-810. Epub 2021 May 14 doi: 10.5551/jat.RV17053. PMID: 33994407Free PMC Article
Finsterer J, Löscher WN, Wanschitz J, Iglseder S
J Neuromuscul Dis 2021;8(1):1-23. doi: 10.3233/JND-200518. PMID: 32986679Free PMC Article
Mercan M, Yayla V, Altinay S, Seyhan S
J Peripher Nerv Syst 2018 Jun;23(2):88-98. Epub 2018 May 8 doi: 10.1111/jns.12265. PMID: 29582519
Schaefer EJ, Anthanont P, Diffenderfer MR, Polisecki E, Asztalos BF
Prog Cardiovasc Dis 2016 Sep-Oct;59(2):97-106. Epub 2016 Aug 24 doi: 10.1016/j.pcad.2016.08.006. PMID: 27565770Free PMC Article
Soumian S, Albrecht C, Davies AH, Gibbs RG
Vasc Med 2005 May;10(2):109-19. doi: 10.1191/1358863x05vm593ra. PMID: 16013195

Therapy

Bonilha I, Luchiari B, Nadruz W, Sposito AC
Arch Endocrinol Metab 2023 Jan 18;67(1):3-18. doi: 10.20945/2359-3997000000585. PMID: 36651718Free PMC Article
Colaco A, Kaya E, Adriaenssens E, Davis LC, Zampieri S, Fernández-Suárez ME, Tan CY, Deegan PB, Porter FD, Galione A, Bembi B, Dardis A, Platt FM
J Inherit Metab Dis 2020 May;43(3):574-585. Epub 2019 Dec 5 doi: 10.1002/jimd.12191. PMID: 31707734Free PMC Article
Puntoni M, Sbrana F, Bigazzi F, Sampietro T
Am J Cardiovasc Drugs 2012 Oct 1;12(5):303-11. doi: 10.2165/11634140-000000000-00000. PMID: 22913675
Soumian S, Albrecht C, Davies AH, Gibbs RG
Vasc Med 2005 May;10(2):109-19. doi: 10.1191/1358863x05vm593ra. PMID: 16013195
Ito T
Drug News Perspect 2003 Oct;16(8):490-2. doi: 10.1358/dnp.2003.16.8.829346. PMID: 14668945

Prognosis

Iqbal J, Al Qarni A, Bakillah A
Adv Exp Med Biol 2022;1372:57-65. doi: 10.1007/978-981-19-0394-6_5. PMID: 35503174
Colaco A, Kaya E, Adriaenssens E, Davis LC, Zampieri S, Fernández-Suárez ME, Tan CY, Deegan PB, Porter FD, Galione A, Bembi B, Dardis A, Platt FM
J Inherit Metab Dis 2020 May;43(3):574-585. Epub 2019 Dec 5 doi: 10.1002/jimd.12191. PMID: 31707734Free PMC Article
Muratsu J, Koseki M, Masuda D, Yasuga Y, Tomoyama S, Ataka K, Yagi Y, Nakagawa A, Hamada H, Fujita S, Hattori H, Ohama T, Nishida M, Hiraoka H, Matsuzawa Y, Yamashita S
J Atheroscler Thromb 2018 Oct 1;25(10):1076-1085. Epub 2018 Mar 20 doi: 10.5551/jat.43257. PMID: 29563393Free PMC Article
Calandra S, Tarugi P, Bertolini S
Curr Opin Lipidol 2011 Apr;22(2):93-9. doi: 10.1097/MOL.0b013e3283426ebc. PMID: 21157333
Soumian S, Albrecht C, Davies AH, Gibbs RG
Vasc Med 2005 May;10(2):109-19. doi: 10.1191/1358863x05vm593ra. PMID: 16013195

Clinical prediction guides

Koseki M, Yamashita S, Ogura M, Ishigaki Y, Ono K, Tsukamoto K, Hori M, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Aug 1;28(8):802-810. Epub 2021 May 14 doi: 10.5551/jat.RV17053. PMID: 33994407Free PMC Article
Hooper AJ, Hegele RA, Burnett JR
Curr Opin Lipidol 2020 Apr;31(2):80-84. doi: 10.1097/MOL.0000000000000669. PMID: 32022754
Muratsu J, Koseki M, Masuda D, Yasuga Y, Tomoyama S, Ataka K, Yagi Y, Nakagawa A, Hamada H, Fujita S, Hattori H, Ohama T, Nishida M, Hiraoka H, Matsuzawa Y, Yamashita S
J Atheroscler Thromb 2018 Oct 1;25(10):1076-1085. Epub 2018 Mar 20 doi: 10.5551/jat.43257. PMID: 29563393Free PMC Article
Schaefer EJ, Anthanont P, Diffenderfer MR, Polisecki E, Asztalos BF
Prog Cardiovasc Dis 2016 Sep-Oct;59(2):97-106. Epub 2016 Aug 24 doi: 10.1016/j.pcad.2016.08.006. PMID: 27565770Free PMC Article
Calandra S, Tarugi P, Bertolini S
Curr Opin Lipidol 2011 Apr;22(2):93-9. doi: 10.1097/MOL.0b013e3283426ebc. PMID: 21157333

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