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hypoalphalipoproteinemia, primary, 1 - Clinical Profile, Genes & Research | Kisho | Kisho

Features include very common findings: Low HDL ("good") cholesterol (decreased hdl cholesterol concentration); and common findings: Premature coronary artery atherosclerosis. 4 total HPO annotations.

Organ System	Phenotype Count	Example Features
Heart and blood vessels	2	Myocardial infarction, Premature coronary artery atherosclerosis
Digestive system	1	Low HDL ("good") cholesterol (decreased hdl cholesterol concentration)

GeneReviews

Clinical Guidance

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, peripheral neuropathy, and hepatosplenomegaly. The clinical course of neuropathy may be either relapsing-remitting or chronic progressive . However, the clinical expression of Tangier disease is variable, with some affected individuals only showing biochemical perturbation.

Histiocytic manifestations

Source: GeneReviews — "Tangier Disease"

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

ABCA1 encodes ATP binding cassette subfamily A member 1 (2,261 aa). Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. Highest expression in Adrenal Gland (54.7 TPM) and Nerve Tibial (33.5 TPM).

Hypoalphalipoproteinemia, primary, 1 is associated with mutations in the ABCA1 gene on chromosome 9.

ABCA1 is classified as a druggable target (Abc Transporter, Cell Surface, Druggable Genome, External Side Of Plasma Membrane, and Transporter categories) with score 0.8.

55 pathogenic variants reported in ABCA1 in ClinVar, including hotspot variants 1326278 and 928660.

Variant	Significance	Review Stars	Hotspot
1326278	Conflicting classifications of pathogenicity	—	Yes
928660	Conflicting classifications of pathogenicity	—	Yes
913117	Conflicting classifications of pathogenicity	—	Yes
913029	Conflicting classifications of pathogenicity	—	Yes
912803	Conflicting classifications of pathogenicity	—	Yes

GeneReviews

Clinical Guidance

Given the small number of individuals with Tangier disease reported in the literature, reliable data on genotype-phenotype correlations are lacking.

Source: GeneReviews — "Tangier Disease"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for hypoalphalipoproteinemia, primary, 1. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Tangier disease, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Tangier Disease

System/Concern	Evaluation	Comment
Histiocytic	Physical exam to assess tonsillar hypertrophy	Consider referral to otolaryngologist. Abdominal ultrasonography to assess for hepatosplenomegaly
Neurologic	Nerve conduction studies electromyography to determine presence /or extent of peripheral neuropathy	Consider referral to neurologist.
Ophthalmologic	Ophthalmologic eval to assess for corneal opacities	Consider referral to ophthalmologist.
Cardiovascular	Plasma lipid profile (total cholesterol, triglycerides, LDL-, HDL-cholesterol) apo A-I concentration	Consider referral to cardiologist. Noninvasive imaging of carotid plaque burden by duplex ultrasonography Coronary calcium score1 /or CT coronary angiography to assess for coronary atherosclerosis
Hematologic	Complete blood count w/differential peripheral blood film (also known as a blood smear)	Consider referral to hematologist.
Dermatologic	Dermatologic consultation if indicated	Miscellaneous/
Other	Consultation w/clinical geneticist /or genetic counselor	Incl genetic counseling A cardiac calcium score involves a noninvasive CT scan of the heart that is able to measure the amount of calcified plaque in the coronary arteries. This score is used to estimate the risk an affected individual has of developing coronary artery disease.
Treatment of Manifestations in Individuals with Tangier Disease Manifestation/Concern	Treatment	Considerations/Other Enlarged hyperplastic
palatine tonsils	Tonsillectomy	Consider if tonsils cause airway obstruction or mass symptoms.
Hepatosplenomegaly	Standard treatment	Incl standard precautions such as avoidance of high-impact sports or activities that could splenic rupture. Abdominal masses may complicate splenectomy. Peripheral
neuropathy	Clinically proven effective treatments are not yet available.	Transient bracing (e.g., w/wrist splint or ankle-foot orthosis) may be useful.
Corneal opacification	Corneal transplantation	Consider if this interferes w/daily living. Coronary artery
disease	Standard treatment, incl use of dietary pharmacologic therapies	See . Thrombocytopenia /
Hemolytic anemia	Standard treatment, if severe	Mitigation of cardiovascular risk factors (including LDL-cholesterol concentrations using statin therapy and a low-fat diet) is indicated. Surveillance Table 5.
Recommended Surveillance for Individuals with Tangier Disease System/Concern	Evaluation	Frequency
Histiocytic	Assessment for hepatosplenomegaly by physical exam abdominal imaging modalities	At each visit
Neurologic	Neurologic eval	Annually Ophthalmologic
Cardiovascular	Cardiovascular risk assessment, incl noninvasive assessment of atherosclerotic plaque burden1	Annually beginning in early adulthood
Hematologic	Complete blood count w/differential	As clinically indicated 1. Duplex coronary ultrasonography (See .

Source: GeneReviews — "Tangier Disease"

GeneReviews

Clinical Guidance

The following should be avoided:

Obesity, because it makes walking more difficult
Medications that are toxic or potentially toxic to persons who are predisposed to the development of peripheral neuropathy, such as vincristine or taxols (paclitaxel)
Contact sports, in those with hepatosplenomegaly

Source: GeneReviews — "Tangier Disease"

GeneReviews

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Tangier Disease"

Clinical Trials

1 trial found

Explore Trials

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with Tangier Disease

System/Concern	Evaluation	Frequency
Histiocytic	Assessment for hepatosplenomegaly by physical exam abdominal imaging modalities	At each visit
Neurologic	Neurologic eval	Annually Ophthalmologic
Cardiovascular	Cardiovascular risk assessment, incl noninvasive assessment of atherosclerotic plaque burden1	Annually beginning in early adulthood
Hematologic	Complete blood count w/differential	As clinically indicated 1. Duplex coronary ultrasonography (See .)

Source: GeneReviews — "Tangier Disease"

Phenotype severity distribution: 1 very common feature, 1 common feature.

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

1 clinical trial registered, 1 recruiting. Interventions under study include other interventions. Pipeline includes 1 NA. Research is primarily sponsored by academic and government institutions.

35 publications have been identified in PubMed for hypoalphalipoproteinemia, primary, 1. Research spans Case Report / Case Series (34%), Epidemiology / Natural History (29%), and Basic Science / Preclinical (20%).

Research Type	Count	% of Total
Patient case studies	12	34%
Disease patterns and progression	10	29%
Laboratory research	7	20%
Research summaries	4	11%
Clinical study results	1	3%
New treatment approaches	1	3%

Recent Publications

Woo YH (2026). [PMID: 41750400](https://pubmed.ncbi.nlm.nih.gov/41750400/). *Biomolecules*. [Gene Therapy / Novel Therapeutics]
Kong Q (2026). [PMID: 42173415](https://pubmed.ncbi.nlm.nih.gov/42173415/). *J Ethnopharmacol*. [Basic Science / Preclinical]
Rodriguez Mori JE (2026). [PMID: 41720735](https://pubmed.ncbi.nlm.nih.gov/41720735/). *Nefrologia (Engl Ed)*. [Case Report / Case Series]
Gómez-Coronado D (2026). [PMID: 41545245](https://pubmed.ncbi.nlm.nih.gov/41545245/). *Journal of clinical lipidology*. [Case Report / Case Series]
Yang Y (2026). [PMID: 41924323](https://pubmed.ncbi.nlm.nih.gov/41924323/). *Clin Nephrol Case Stud*. [Case Report / Case Series]
Hegele RA (2026). [PMID: 42095752](https://pubmed.ncbi.nlm.nih.gov/42095752/). *Expert Opin Ther Targets*. [Review / Meta-Analysis]
Guo J (2026). [PMID: 41187527](https://pubmed.ncbi.nlm.nih.gov/41187527/). *J Diabetes Complications*. [Epidemiology / Natural History]
Farkas GJ (2025). [PMID: 40363903](https://pubmed.ncbi.nlm.nih.gov/40363903/). *J Clin Med*. [Review / Meta-Analysis]
Vatakencherry RMJ (2025). [PMID: 40726653](https://pubmed.ncbi.nlm.nih.gov/40726653/). *J Family Med Prim Care*. [Epidemiology / Natural History]
Fischer T (2025). [PMID: 41126187](https://pubmed.ncbi.nlm.nih.gov/41126187/). *Lipids Health Dis*. [Epidemiology / Natural History]

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hypoalphalipoproteinemia, primary, 1

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Questions for Your Care Team

Questions for Your Care Team

hypoalphalipoproteinemia, primary, 1

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Related Diseases

Questions for Your Care Team

Questions for Your Care Team