Genomic coordinates (9:104,781,006 human ABCA1) & ( 4:53,030,787 mouse Abca1).
Here I present: “Tangier Disease“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (ABCA1) 唐吉爾氏症 。icd10=E78.6
INTRODUCTION.
Tangier disease 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.
Tangier disease (familial HDL deficiency) is a autosomal-recessive lipid disorder caused by mutations in ABCA1, leading to extremely low HDL cholesterol and impaired cholesterol efflux from cells.
Key Features.
Very low/absent HDL
HDL often <5 mg/dL.
Orange-yellow enlarged tonsils. Classic finding due to cholesterol-laden macrophages.
Peripheral neuropathy. Sensory neuropathy is common.
Hepatosplenomegaly & lymphadenopathy.
Corneal opacities.
Atherosclerosis risk,
increased risk of premature cardiovascular disease, but variable.
Genetics & Pathophysiology.
Gene: ABCA1 ( ATP-binding cassette transporter-A1)
Inheritance: Autosomal recessive.
Mechanism:
ABCA1 normally transfers cholesterol from peripheral cells → ApoA-I → HDL formation. In Tangier disease, impaired efflux → cholesterol esters accumulate in reticuloendothelial cells.
There is evidence that Tangier disease is caused by mutation of the ATP-Binding Cassette submember-A, family-1 (ABCA1) gene encoded in humans on cytogenetic location 9q31.1 and genomic coordinate 9:104,781,006.
The ATP-Binding Cassette submember-A, family-1 (ABCA1) gene functions as a cholesterol efflux pump in the cellular lipid removal pathway.
