Tangier Disease

An autosomal recessively inherited disorder caused by mutation of ATP-BINDING CASSETTE TRANSPORTERS involved in cellular cholesterol removal (reverse-cholesterol transport). It is characterized by near absence of ALPHA-LIPOPROTEINS (high-density lipoproteins) in blood. The massive tissue deposition of cholesterol esters results in HEPATOMEGALY; SPLENOMEGALY; RETINITIS PIGMENTOSA; large orange tonsils; and often sensory POLYNEUROPATHY. The disorder was first found among inhabitants of Tangier Island in the Chesapeake Bay, MD.

Also Known As:

Alpha High Density Lipoprotein Deficiency Disease; Cholesterol Thesaurismosis; HDLDT1; High Density Lipoprotein Deficiency, Tangier Type; High Density Lipoprotein Deficiency, Type 1; High-Density Lipoprotein Deficiency, Tangier Type; High-Density Lipoprotein Deficiency, Type I; Neuropathy of Tangier Disease; Tangier Hereditary Neuropathy; A-alphalipoprotein Neuropathies; Analphalipoproteinemias; Cholesterol Thesaurismoses; High Density Lipoprotein Deficiency, Type I; Neuropathies, A-alphalipoprotein; Neuropathy, A-alphalipoprotein; Thesaurismoses, Cholesterol; Thesaurismosis, Cholesterol; A-alphalipoprotein Neuropathy; Analphalipoproteinemia; Tangier Disease Neuropathy

Networked: 408 relevant articles (10 outcomes, 28 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Lecithin Cholesterol Acyltransferase Deficiency (Lecithin:Cholesterol Acyltransferase Deficiency)
2.	Atherosclerosis
3.	Mononeuropathies (Mononeuritis Multiplex)
4.	Lamellar Ichthyosis (Harlequin Ichthyosis)
5.	Skin Diseases (Skin Disease)

Experts

1.	Hayden, Michael R: 9 articles (01/2015 - 10/2002)
2.	Genest, Jacques: 9 articles (10/2006 - 12/2002)
3.	Parks, John S: 7 articles (10/2017 - 05/2005)
4.	Marcil, Michel: 7 articles (10/2006 - 12/2002)
5.	Krimbou, Larbi: 7 articles (07/2005 - 12/2002)
6.	Oram, J F: 7 articles (10/2001 - 04/2000)
7.	Yamashita, Shizuya: 6 articles (08/2021 - 08/2002)
8.	Remaley, Alan T: 6 articles (08/2010 - 04/2003)
9.	Ueda, Kazumitsu: 6 articles (09/2009 - 08/2002)
10.	Tall, Alan R: 5 articles (01/2018 - 01/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Tangier Disease:

1.	LipidsIBA 05/01/2006 - "Pathological studies of a sural nerve biopsy in a man with Tangier disease presenting as a remitting-relapsing multifocal neuropathy showed abnormalities in the paranodal regions, including lipid deposition (65%) and redundant myelin foldings, with various degrees of myelin splitting and vesiculation (43%) forming small tomacula and abnormal myelin terminal loops (4%). " 03/01/1978 - "Adult-onset of Tangier disease: 1. Morphometric and pathologic studies suggesting delayed degradation of neutral lipids after fiber degeneration." 01/01/2016 - "The characteristic lipid profile of Tangier disease was noted in this patient viz. " 10/01/2014 - "Lipid profile was compatible with Tangier disease (TD). " 01/01/2011 - "In this case report we describe a patient with diabetes who experienced an episode of urosepsis with a plasma lipid profile resembling Tangier disease. "
2.	Apolipoprotein A-I (Apolipoprotein A1)IBA 12/01/1987 - "Therefore, the relative increase in proapoA-I in Tangier disease is due to a marked decrease in mature apoA-I resulting from rapid catabolism of both pro- and mature apoA-I and not to defective conversion of proapoA-I to mature apoA-I." 04/03/2003 - "Our studies of apo A-I-containing HDL subpopulations in various patient populations reveal that patients homozygous for Tangier disease have only the pre-beta(1) HDL subspecies. " 11/01/2008 - "Blocking ABCA1 with an anti-ABCA1 antibody abolished the effect of apoA-I. Furthermore, monocytes derived from a Tangier disease patient definitively confirmed the requirement of ABCA1 in apoA-I-mediated CD11b inhibition. " 10/26/2001 - "ApoA-I lacked the ability to remove alpha-TOH from Tangier disease fibroblasts that have a nonfunctional ABCA1. " 01/01/1994 - "Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia."
3.	CholesterolIBA 05/01/2003 - "Unlike patients with Tangier disease, cholesterol efflux was found to be normal under the experimental conditions used in the present study. " 12/01/1983 - "The results of this study indicate that normal serum cholesterol levels do not exclude a diagnosis of Tangier disease. " 11/01/2021 - "Tangier disease is a rare autosomal recessive disease resulting in cholesterol deposition in different organs. " 01/01/2015 - "In a remarkably large Tangier disease pedigree with four affected siblings, we identified compound heterozygosity for previously reported missense variants, p.Arg937Val and p.Thr940Met, and show that both of these mutations result in significantly impaired cholesterol efflux in transfected cells. " 12/27/2013 - "The Tangier disease W590S ABCA1 mutation has defective PS floppase activity and diminished cholesterol efflux activity. "
4.	ApolipoproteinsIBA 12/15/2000 - "The impairment of the apolipoprotein-mediated reaction was found in Tangier disease and other familial HDL deficiencies to strongly suggest that this is a main mechanism to produce plasma HDL. " 05/01/1995 - "Survey of the family led to the discovery of one sister, with asymptomatic apolipoprotein Al deficiency and a normal sister, while the parents were heterozygotes for Tangier disease. " 01/01/1987 - "Plasma apolipoproteins in Tangier disease, as studied with two-dimensional electrophoresis." 01/15/1979 - "Charge-shift electrophoresis of apolipoproteins from normal humans and patients with Tangier disease." 09/01/1993 - "This study establishes that a form of severe hypoalphalipoproteinemia distinct from Tangier disease can be caused by marked hypercatabolism of a normal A-I apolipoprotein."
5.	HDL LipoproteinsIBA 05/26/1986 - "Immunochemical study of the plasma low and high density lipoproteins in Tangier disease." 12/01/2014 - "Tangier disease is an extremely rare and severe form of high density lipoprotein deficiency. " 10/01/2012 - "Tangier disease is one of the most severe forms of familial high-density lipoprotein (HDL) deficiency. " 06/01/2012 - "Tangier disease (TD) (OMIM#205400) is a rare autosomal recessive disorder resulting from mutations in the ABCA1 gene, leading to decreased levels of plasma high-density lipoproteins (HDL). " 08/01/2010 - "ABCA1 became a primary subject of research in many academic and pharmaceutical laboratories immediately after the discovery that mutations at the gene locus cause severe familial High Density Lipoprotein (HDL) deficiency and, in the homozygous form - Tangier disease. "
6.	ATP-Binding Cassette Transporters (ABC Transporters)IBA 02/15/2023 - "ATP-binding cassette transporter A1 (ABCA1) has been identified as the molecular defect in Tangier disease. " 01/01/2019 - "Using the example of the ATP-binding cassette transporter A1 (ABCA1) gene (Tangier disease), we describe our algorithm for functionally significant sequence finding. " 01/01/2019 - "ATP-binding cassette transporter A1 (ABCA1) gene mutations in a patient with Tangier disease, who presented an uncommon clinical history, and in his family were found and characterized. " 07/01/2018 - "Homozygous variations in ATP-binding cassette transporter A1 typically cause Tangier disease, a rare autosomal recessive condition linked with several other abnormalities (eg, enlarged discolored tonsils). " 09/18/2014 - "Tangier disease (TD) is a rare autosomal recessive disorder, resulting from mutations in the ATP binding cassette transporter (ABCA1) gene. "
7.	ApoproteinsIBA 02/01/1982 - "Clinically FED differs from other familial conditions with deficiency of HDL such as Tangier disease, LCAT-deficiency and Milano-AI-apoprotein disease. " 07/01/1995 - "Thus, apoA-I could be initially secreted as a family of particles that are rapidly cleared from plasma, and a portion of this apoprotein then reappears in a slowly turning-over pool that constitutes the major mass of apoA-I. The physiologic identity of these kinetically distinct apoA-I species is unknown; however, the fast pool of apoA-I demonstrated in these studies is strikingly similar to that seen in subjects with Tangier disease who lack the slow pool." 03/01/1977 - "In this study we have determined by radioimmunoassay and double immunoelectrophoresis the total quantities and distributions of A apoproteins in three adult patients affected with Tangier disease (hereditary alpha-lipoprotein deficiency). " 03/01/1977 - "The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins." 12/28/1978 - "The low levels of apoA-I in Tangier disease are not due to a failure of intestinal synthesis but might be due to abnormal metabolism of chylomicron apoproteins."
8.	Proteins (Proteins, Gene)FDA Link 10/01/1972 - "Studies on the protein defect in Tangier disease. " 10/01/2006 - "However, we identified a novel frameshift mutation (F1840L, L1869X); a proband was heteroallelic for the N1800H mutation, previously reported in a case of Tangier disease, and a novel missense mutation (Q2210H); a novel variant (G616V), predicted to impart a functional defect in the protein, was also found in another proband. " 03/07/2003 - "The three different mutants in the first extracellular domain of human ABCA1 associated with Tangier disease, R587W, W590S, and Q597R, were examined for their subcellular localization and function by using ABCA1-GFP fusion protein stably expressed in HEK293 cells. " 03/01/2001 - "[Tangier disease and ABC proteins]." 04/01/1985 - "Urinary proteins in a patient with Tangier disease."
9.	miglustat (Zavesca)FDA Link 01/01/2020 - "When a Tangier disease patient was misdiagnosed with NPC and treated with miglustat, her symptoms improved. " 09/18/2014 - "Effects of miglustat treatment in a patient affected by an atypical form of Tangier disease." 01/01/2020 - "In addition, this study further supports the hypothesis that miglustat, as well as other substrate reduction therapies, may be potential therapeutic agents for treating Tangier disease as fibroblasts from multiple Tangier patients were corrected by miglustat treatment." 01/01/2020 - "Tangier disease is currently without therapy, whereas NPC can be treated with miglustat, a small molecule inhibitor of glycosphingolipid biosynthesis that slows the neurological course of the disease. "
10.	Phospholipids (Phosphatides)FDA LinkGeneric 08/01/2010 - "In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. " 02/01/2001 - "Cellular cholesterol efflux is modulated by phospholipid-derived signaling molecules in familial HDL deficiency/Tangier disease fibroblasts." 05/01/1998 - "Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I." 01/01/2019 - "Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. " 01/01/2003 - "ABCA1, the defective molecule in Tangier disease, mediates the efflux of phospholipids and cholesterol from cells to apoA-I, reversing foam cell formation. "

Therapies and Procedures

1.	Therapeutics 01/01/2020 - "Advances have been made in the study of the neurological abnormalities observed in Tangier disease, both in their assessment and the identification of potential new therapies. " 12/01/2014 - "Even though there is no specific therapy for patients with Tangier disease, it is important to recognize the clinical presentation as patients are at an increased risk of developing atherosclerosis and subsequent CVD. " 01/01/2020 - "In addition, this study further supports the hypothesis that miglustat, as well as other substrate reduction therapies, may be potential therapeutic agents for treating Tangier disease as fibroblasts from multiple Tangier patients were corrected by miglustat treatment." 01/01/2020 - "Tangier disease is currently without therapy, whereas NPC can be treated with miglustat, a small molecule inhibitor of glycosphingolipid biosynthesis that slows the neurological course of the disease. "
2.	Ligation 12/01/2009 - "The data demonstrated that Ssp DnaE intein can efficiently catalyze the ligation of ABCA1 providing an evidence for our ongoing study on ABCA1 gene transfer by a dual AAV vector system to circumvent AAV volume limitation in gene therapy of Tangier disease which resulted from ABCA1 gene mutations."
3.	Plasma Exchange 06/01/1978 - "High density lipoprotein (HDL) infusion and partial plasma exchange were undertaken in two patients homozygous for Tangier disease. " 06/01/1978 - "High density lipoprotein infusion and partial plasma exchange in Tangier disease." 02/01/1981 - "The metabolism of apolipoproteins A-I and A-II, as well as other high density lipoprotein (HDL) constituents, was studied in patients with homozygous familial HDL deficiency (Tangier disease) prior to and after plasma exchange or HDL infusion. "
4.	Coronary Artery Bypass (Coronary Artery Bypass Surgery) 09/01/2002 - "Coronary artery bypass grafting for a patient with Tangier disease." 08/01/1992 - "Cardiac necropsy findings are described in a 72-year-old man with Tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. "
5.	Slit Lamp 11/01/2004 - "Confocal microscopy helps to identify corneal changes in the stroma caused by Tangier disease easily missed in a slit-lamp examination. "