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:

Networked: 362 relevant articles (10 outcomes, 23 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Lecithin Acyltransferase Deficiency (Lecithin:Cholesterol Acyltransferase Deficiency)
2.	Atherosclerosis
3.	Macular Degeneration (Age-Related Maculopathy)
4.	Mononeuropathies (Mononeuritis Multiplex)
5.	Lamellar Ichthyosis (Harlequin Ichthyosis)

Experts

1.	Hayden, Michael R: 9 articles (01/2015 - 10/2002)
2.	Genest, Jacques: 9 articles (10/2008 - 12/2002)
3.	Krimbou, Larbi: 7 articles (07/2005 - 12/2002)
4.	Oram, J F: 7 articles (10/2001 - 04/2000)
5.	Ueda, Kazumitsu: 6 articles (09/2015 - 08/2002)
6.	Parks, John S: 6 articles (06/2012 - 05/2005)
7.	Remaley, Alan T: 6 articles (08/2010 - 04/2003)
8.	Marcil, Michel: 6 articles (05/2004 - 12/2002)
9.	Brunham, Liam R: 5 articles (01/2015 - 11/2004)
10.	Calandra, Sebastiano: 5 articles (01/2014 - 02/2003)

Drugs and Biologics

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

1.	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."
2.	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. " 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 - "Depletion of sphingomyelin in stably transfected HEK293 cells expressing the Tangier disease W590S mutant ABCA1 isoform rescued the defect in PS exposure and restored cholesterol efflux to apoAI. " 12/27/2013 - "The Tangier disease W590S ABCA1 mutation has defective PS floppase activity and diminished cholesterol efflux activity. "
3.	ApolipoproteinsIBA 10/01/1999 - "The severely impaired apolipoprotein-mediated lipid removal pathway in Tangier disease fibroblasts, which persisted after immortalization, was not improved by treatment with a cAMP analog, implying that the cellular defect in Tangier disease is upstream from this cAMP-dependent signaling pathway.These" 05/14/2004 - "Tangier disease (TD) is a human genetic disorder associated with defective apolipoprotein-I-induced lipid efflux and increased atherosclerotic susceptibility. " 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. " 04/01/2000 - "Moreover, formation of these structures was nearly absent in fibroblasts from a subject with Tangier disease, cells that lack a functioning apolipoprotein-mediated lipid removal pathway. " 10/01/1999 - "The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway."
4.	Lipoproteins (Lipoprotein)IBA 05/01/2012 - "These studies highlight a novel role for hepatic ABCA1 in the metabolism of all three major classes of plasma lipoproteins and provide a metabolic link between elevated TG and reduced HDL levels that are a common feature of Tangier disease, MS, and T2D. " 01/15/2016 - "Subfraction analysis of circulating lipoproteins in a patient with Tangier disease due to a novel ABCA1 mutation." 10/01/2012 - "Tangier disease is one of the most severe forms of familial high-density lipoprotein (HDL) deficiency. " 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. " 05/01/2010 - "Tangier disease (TD) is a rare autosomal recessive disorder characterized by a deficiency or absence of high-density lipoprotein (HDL) caused by mutations in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1). "
5.	Adenosine Triphosphate (ATP)IBA 01/01/2014 - "Tangier disease (TD) is a rare autosomal recessive disorder, resulting from mutations in the ATP binding cassette transporter (ABCA1) gene. " 10/01/2012 - "Tangier disease is caused by mutations in the 'ATP-Binding Cassette transporter A1' (ABCA1) gene, which encodes the membrane transporter ABCA1. " 04/01/2010 - "In Tangier disease, absence of ATP binding cassette transporter A1 (ABCA1) results in reduced plasma HDL and elevated triglyceride (TG) levels. " 03/01/2008 - "Tangier disease (TD) is a rare familial disorder with mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. " 08/01/2006 - "A new mutation (R1068H) within the first ATP-binding domain was identified in homozygous form in the Tangier disease individual and was present in several family members. "
6.	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). " 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." 03/01/1977 - "The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins."
7.	Phosphatidylcholines (Phosphatidylcholine)IBA 11/15/1996 - "Defective regulation of phosphatidylcholine-specific phospholipases C and D in a kindred with Tangier disease. " 04/01/1997 - "Membrane lipid abnormalities included hereditary high red cell membrane phosphatidylcholine hemolytic anemia (30 patients from 18 kindreds), congenital beta-lipoprotein deficiency (acanthocytosis: seven patients from five kindreds), and each one patient of congenital lecithin: cholesterol acyltransferase deficiency and of congenital alpha-lipoprotein deficiency (Tangier disease)." 09/07/2011 - "For example, mutations in ABCA1 cause Tangier disease associated with defective efflux of cholesterol and phosphatidylcholine from the plasma membrane to the lipid acceptor protein apoA1 (apolipoprotein AI), mutations in ABCA3 cause neonatal surfactant deficiency associated with a loss in secretion of the lipid pulmonary surfactants from lungs of newborns, mutations in ABCA4 cause Stargardt macular degeneration, a retinal degenerative disease linked to the reduced clearance of retinoid compounds from photoreceptor cells, mutations in ABCA12 cause harlequin and lamellar ichthyosis, skin diseases associated with defective lipid trafficking in keratinocytes, and mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial hepatic disease and sitosterolaemia associated with defective phospholipid and sterol transport respectively. "
8.	Telomerase (Telomerase Reverse Transcriptase)IBA 12/27/2013 - "In summary, these results may help to understand the differential atherosclerotic susceptibility in Tangier disease and further demonstrate the usefulness of telomerase-immortalized cells in studying this cellular phenotype. " 12/27/2013 - "Characterization of cholesterol homeostasis in telomerase-immortalized Tangier disease fibroblasts reveals marked phenotype variability." 05/14/2004 - "The establishment of telomerase-immortalized Tangier disease cell lines indicates the existence of an apolipoprotein A-I-inducible but ABCA1-independent cholesterol efflux pathway."
9.	Ca(2+) Mg(2+)-ATPaseIBA 07/01/1984 - "A significant reduction of endoneurial Na+,K+-ATPase and Mg2+-ATPase activities was shown in six sural nerve biopsies from patients with Tangier disease complicated by mononeuropathy multiplex or progressive axonal neuropathy. "
10.	Retinaldehyde (Retinal)IBA 09/07/2011 - "For example, mutations in ABCA1 cause Tangier disease associated with defective efflux of cholesterol and phosphatidylcholine from the plasma membrane to the lipid acceptor protein apoA1 (apolipoprotein AI), mutations in ABCA3 cause neonatal surfactant deficiency associated with a loss in secretion of the lipid pulmonary surfactants from lungs of newborns, mutations in ABCA4 cause Stargardt macular degeneration, a retinal degenerative disease linked to the reduced clearance of retinoid compounds from photoreceptor cells, mutations in ABCA12 cause harlequin and lamellar ichthyosis, skin diseases associated with defective lipid trafficking in keratinocytes, and mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial hepatic disease and sitosterolaemia associated with defective phospholipid and sterol transport respectively. "

Therapies and Procedures

1.	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."
2.	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. "
3.	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. "
4.	Splenectomy 09/01/1983 - "Massive omental reticuloendothelial cell lipid uptake in Tangier disease after splenectomy." 09/01/1983 - "The spleen appears to play a significant role in the removal of abnormal lipoproteins in Tangier homozygotes; therefore, splenectomy may be contraindicated in Tangier disease."
5.	Anesthesia 04/01/2000 - "[Anesthesia for MIDCAB (minimally invasive direct coronary bypass) in a patient with Tangier disease: a case report]."