Lecithin cholesterol acyltransferase deficiency

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Lecithin cholesterol acyltransferase deficiency
Other namesLCAT deficiency
SpecialtyMedical genetics Edit this on Wikidata

Lecithin cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism.[1] The disease has two forms:[2] Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency.[3]

cholesterol esters
in lipoproteins.

Signs and symptoms

Symptoms of the familial form include visual impairment caused by diffuse corneal opacities, target cell hemolytic anemia, and kidney failure. Less common symptoms include atherosclerosis, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), and enlarged lymph nodes.[4]

Fish-eye disease is less severe and most commonly presents with impaired vision due to corneal opacification. It rarely presents with other findings, although, atherosclerosis, hepatomegaly, splenomegaly, and lymphadenopathy can occur.[4] Carlson and Philipson found that the disease was named so because the cornea of the eye was so opaque or cloudy with dots of cholesterol that it resembled a boiled fish.[5]

If an individual only carries one copy of the mutated gene, they typically do not show symptoms.[6]

Pathophysiology

A deficiency of LCAT causes accumulation of unesterified cholesterol in certain body tissues. Cholesterol effluxes from cells as free cholesterol and is transported in HDL as esterified cholesterol. LCAT is the enzyme that esterifies the free

apolipoprotein A2. The remaining form of HDL resembles nascent HDL.[citation needed
]

The LCAT

low density lipoproteins (LDL).[7] The opaqueness of the eye is caused by the deposit of lipids onto the cornea.[7]

Diagnosis

Definitive diagnosis requires LCAT gene analysis for mutation and functional activity. However, numerous lab tests may help with making a diagnosis such as complete blood count (CBC), urinalysis, blood chemistries, lipid panels, and plasma LCAT activity.[8]

Fish-eye disease is characterized by abnormalities like visual impairment, plaques of fatty material, and dense opacification.[5][7]

Types

Both the familial type and Fish-eye disease are

LCAT gene located on chromosome 16q22.1, which is the long (q) arm of chromosome 16 a position 22.1.[7] Both diseases are very rare with ~70 reported cases of familial LCAT deficiency[9] and ~30 cases of fish-eye disease.[10]

Familial LCAT Deficiency Lab Findings

  • CBC: normochromic normocytic anemia
  • Urinalysis: proteinuria in young adults (suggestive of kidney failure)
  • Blood Chemistries: elevated blood urea nitrogen (BUN) and creatinine (suggestive of kidney failure)
  • Lipid Panel: low high-density lipoprotein (HDL) < 10 mg/dL, elevated very low-density lipoprotein (VLDL) and triglycerides, high plasma unesterified cholesterol, and low plasma cholesterol ester
  • Plasma LCAT activity: decreased (determined by decreased ability to esterify radioactive cholesterol in exogenous lipoproteins)

Fish-eye Disease Lab Findings

  • CBC: no anemia
  • Urinalysis: no protein in the urine
  • Blood Chemistries: normal blood urea nitrogen (BUN) and creatinine (no signs of kidney failure)
  • Lipid Panel: low high-density lipoprotein (HDL) < 10 mg/dL, elevated very low-density lipoprotein (VLDL) and triglycerides, high plasma unesterified cholesterol in HDL particles, and low cholesterol ester in HDL particles but normal levels in low-density lipoprotein (LDL) and VLDL particles
  • Plasma LCAT activity: decreased only in HDL particles but not LDL

Genetic Findings in Fish-eye Disease

Mutations in the LCAT gene, which is localized in the q21–22 region of

homozygous for a Thr123→Ile mutation or Pro10→Leu mutation.[11] New mutations have been identified as homozygosity for an A2205→G nucleotide substitution in exon 4 of the LCAT gene which is predicted to be the cause of an Asp131→Asn substitution.[7]

Treatment

Currently, there is no specific treatment to correct the LCAT deficiency so therapy is focused on symptom relief.

kidney transplant may be considered.[citation needed
]

Prognosis

Kidney failure is the major cause of morbidity and mortality in complete LCAT deficiency, while in partial deficiency (fish eye disease) major cause of morbidity is visual impairment due to corneal opacity. These patients have low HDL cholesterol but surprisingly premature atherosclerosis is not seen. However, there are some reported cases.[citation needed]

References

  1. PMID 9162740
    .
  2. PMID 15994445
    .
  3. ^
    S2CID 27089164
    .
  4. ^ a b "Lecithin-Cholesterol Acyltransferase Deficiency: Overview, Presentation, Differential Diagnosis". 2016-08-08. {{cite journal}}: Cite journal requires |journal= (help)
  5. ^
    PMID 9162740
    .
  6. ^ Kaneshiro, N.K. (2014). "Autosomal Recessive". National Institutes of Health, Medline Plus.
  7. ^
    PMID 8675648
    .
  8. ^ "Lecithin-Cholesterol Acyltransferase Deficiency: Overview, Presentation, Differential Diagnosis". 2016-08-08. {{cite journal}}: Cite journal requires |journal= (help)
  9. ^ Reference, Genetics Home. "complete LCAT deficiency". Genetics Home Reference. Retrieved 2016-12-11.
  10. ^ Reference, Genetics Home. "fish-eye disease". Genetics Home Reference. Retrieved 2016-12-11.
  11. PMID 8820100
    .
  12. ^ "Fish-eye disease | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.

External links

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