"What is familial LCAT deficiency?
Does HDL-cholesterol in blood decrease to less than 20 mg/dL[*1]?"
Supervised by: Kotaro Yokote, Diabetes, Metabolism & Endocrinology, Chiba University Hospital
Cholesterol is indispensable to keeping the body in good working order. However, too much cholesterol caused by excessive intake of fat can be harmful to the body and consequently is taken into a high-density lipoprotein (HDL) called “good” cholesterol and sent to the liver via the blood. To facilitate the transfer of unnecessary cholesterol to the liver via HDL, an enzyme called LCAT（Lecithin cholesterol acyltransferase) is necessary. In fact, without LCAT, the unnecessary cholesterol cannot be processed and instead accumulates in various tissue throughout the body, where it can lead to disease.
Familial LCAT deficiency is a disease in which the body is unable to make the LCAT protein (or unable to make enough) because it lacks the gene necessary to produce LCAT. Individuals may be born without the gene or may suffer a genetic abnormality. Patients with LCAT deficiency are unable to transfer unnecessary cholesterol to HDL for processing in the liver. Consequently, the HDL-cholesterol level in the blood decreases significantly, while excess cholesterol accumulates in the eyes and in the kidneys. This will cause cloudy corneal (clouding of the clear covering of the eye and deteriorating vision), renal dysfunction (impairment of the kidneys preventing elimination of waste in addition to the presence of urinary protein), and hemolytic anemia (anemic symptoms such as heart palpitations, short breath, and dizziness, as well as jaundice). Advanced renal dysfunction can lead to the accumulation of a variety of harmful substances in the body, causing even more adverse effects (increased blood pressure, anemic symptoms, heart failure, uremia, electrolyte imbalance in blood, etc.).
Familial LCAT deficiency was designated as an “intractable” disease by the Ministry of Health, Labour and Welfare (MHLW) on July 1, 2015 (notification number 259).
[*1]When familial LCAT deficiency was designated as an intractable disease by the MHLW on July 1, 2015, the diagnostic criteria for this disease specified the HDL-cholesterol level as less than 10 mg/dL. Since then, however, patients with HDL-cholesterol between 10 mg/dL and 20 mg/dL have also been diagnosed with familial LCAT deficiency.
Treatment of familial LCAT deficiency
As of now there is no radical therapy for this disease. Dietary and lifestyle changes are usually advocated such as low-fat diet therapy to limit the intake of fat from food. By controlling the amount of cholesterol in the body, the accumulation of excess cholesterol can be reduced to delay the occurrence of corneal clouding, renal dysfunction, and hemolytic anemia. The symptoms can be alleviated by administering dialysis to patients with aggravated conditions caused by renal dysfunction. This is not considered a radical therapy.
The following is an excerpt from “259. LCAT deficiency — appendix, summary, therapeutic criteria, etc.” on the MHLW webpage.
“4. Therapeutic Method: There is no radical therapy established as of now. Research into gene therapy using LCAT pre-transgenic adipocyte transplant for classical LCAT deficiency is underway.”
Gene therapy using LCAT pre-transgenic adipocyte transplant
An enzyme replacement therapy using LCAT pre-transgenic adipocyte has been developed at Chiba University. A physician-led test is now being conducted at Chiba University targeting patients with familial LCAT deficiency.