Recent from talks
Lysosomal acid lipase deficiency
Knowledge base stats:
Talk channels stats:
Members stats:
Lysosomal acid lipase deficiency
Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) or Wolman disease, is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an important role in breaking down fatty material (cholesteryl esters and triglycerides) in the body. Infants, children, and adults who have LAL deficiency experience a range of serious health problems. The lack of the LAL enzyme can lead to a build-up of fatty material in several body organs, including the liver, spleen, gut, the wall of blood vessels, and other important organs.
The classic presentation is vomiting and failure to thrive or failure to gain weight in a newborn, with chalky bilateral adrenal calcifications on imaging, with life expectancy rarely exceeding a year. Very low levels of the LAL enzyme lead to LAL deficiency. LAL deficiency typically affects infants in the first year of life. The accumulation of fat in the walls of the gut in early-onset disease leads to serious digestive problems, including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age (failure to thrive). As the disease progresses, it can cause life-threatening liver dysfunction or liver failure.
Infants are chronically ill from birth, and rarely survive beyond the first year of life. In 2015, an enzyme replacement therapy, sebelipase alfa, was approved in the US and EU. The therapy was additionally approved in Japan in 2016.
Infants may present with feeding difficulties, with frequent vomiting, diarrhea, swelling of the abdomen, and failure to gain weight or sometimes weight loss.
As the disease progresses in infants, increasing fat accumulation in the liver leads to other complications, including yellowing of the skin and whites of the eyes (jaundice), and a persistent low-grade fever. An ultrasound examination shows an accumulation of chalky material (calcification) in the adrenal gland in about half of infants with LAL-D. Complications of LAL-D progress over time, eventually leading to life-threatening problems, such as extremely low levels of circulating red blood cells (severe anemia), liver dysfunction or failure, and physical wasting (cachexia).
Older children or adults generally present with a wide range of signs and symptoms that overlap with other disorders. They may have diarrhoea, stomach pain, vomiting, or poor growth, a sign of malabsorption. They may have signs of bile-duct problems, like itchiness, jaundice, pale stool, or dark urine. Their feces may be excessively greasy. They often have an enlarged liver, liver disease, and may have yellowish deposits of fat underneath the skin, usually around their eyelids. The disease is often undiagnosed in adults. The person may have a history of premature cardiac disease or premature stroke.
Lysosomal acid lipase deficiency is a genetic disease that is autosomal recessive. It is an inborn error of metabolism that causes a lysosomal storage disease. The condition is caused by a mutation of the LIPA gene, which encodes the lysosomal lipase protein (also called lysosomal acid lipase or LAL), that results in a loss of the protein's normal function. When LAL functions normally, it breaks down cholesteryl esters and triglycerides in low-density lipoprotein particles into free cholesterol and free fatty acids that the body can reuse; when LAL does not function, cholesteryl esters and triglycerides build up in the liver, spleen, and other organs. The accumulation of fat in the walls of the gut and other organs in leads to serious digestive problems, including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food, persistent and often forceful vomiting, frequent diarrhea, foul-smelling and fatty stools (steatorrhea), and failure to grow.
Lysosomal acid lipase deficiencies occur when a person has defects (mutations) in both copies of the LIPA gene. Each parent of a person with LAL-D carries one copy of the defective LIPA gene. With every pregnancy, parents with a son or daughter affected by LAL deficiency have a one in four (25%) chance of having another affected child. A person born with defects in both LIPA genes is not able to produce adequate amounts of the LAL enzyme.
Hub AI
Lysosomal acid lipase deficiency AI simulator
(@Lysosomal acid lipase deficiency_simulator)
Lysosomal acid lipase deficiency
Lysosomal acid lipase deficiency (LAL deficiency or LAL-D) or Wolman disease, is an autosomal recessive inborn error of metabolism that results in the body not producing enough active lysosomal acid lipase (LAL) enzyme. This enzyme plays an important role in breaking down fatty material (cholesteryl esters and triglycerides) in the body. Infants, children, and adults who have LAL deficiency experience a range of serious health problems. The lack of the LAL enzyme can lead to a build-up of fatty material in several body organs, including the liver, spleen, gut, the wall of blood vessels, and other important organs.
The classic presentation is vomiting and failure to thrive or failure to gain weight in a newborn, with chalky bilateral adrenal calcifications on imaging, with life expectancy rarely exceeding a year. Very low levels of the LAL enzyme lead to LAL deficiency. LAL deficiency typically affects infants in the first year of life. The accumulation of fat in the walls of the gut in early-onset disease leads to serious digestive problems, including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food. Because of these digestive complications, affected infants usually fail to grow and gain weight at the expected rate for their age (failure to thrive). As the disease progresses, it can cause life-threatening liver dysfunction or liver failure.
Infants are chronically ill from birth, and rarely survive beyond the first year of life. In 2015, an enzyme replacement therapy, sebelipase alfa, was approved in the US and EU. The therapy was additionally approved in Japan in 2016.
Infants may present with feeding difficulties, with frequent vomiting, diarrhea, swelling of the abdomen, and failure to gain weight or sometimes weight loss.
As the disease progresses in infants, increasing fat accumulation in the liver leads to other complications, including yellowing of the skin and whites of the eyes (jaundice), and a persistent low-grade fever. An ultrasound examination shows an accumulation of chalky material (calcification) in the adrenal gland in about half of infants with LAL-D. Complications of LAL-D progress over time, eventually leading to life-threatening problems, such as extremely low levels of circulating red blood cells (severe anemia), liver dysfunction or failure, and physical wasting (cachexia).
Older children or adults generally present with a wide range of signs and symptoms that overlap with other disorders. They may have diarrhoea, stomach pain, vomiting, or poor growth, a sign of malabsorption. They may have signs of bile-duct problems, like itchiness, jaundice, pale stool, or dark urine. Their feces may be excessively greasy. They often have an enlarged liver, liver disease, and may have yellowish deposits of fat underneath the skin, usually around their eyelids. The disease is often undiagnosed in adults. The person may have a history of premature cardiac disease or premature stroke.
Lysosomal acid lipase deficiency is a genetic disease that is autosomal recessive. It is an inborn error of metabolism that causes a lysosomal storage disease. The condition is caused by a mutation of the LIPA gene, which encodes the lysosomal lipase protein (also called lysosomal acid lipase or LAL), that results in a loss of the protein's normal function. When LAL functions normally, it breaks down cholesteryl esters and triglycerides in low-density lipoprotein particles into free cholesterol and free fatty acids that the body can reuse; when LAL does not function, cholesteryl esters and triglycerides build up in the liver, spleen, and other organs. The accumulation of fat in the walls of the gut and other organs in leads to serious digestive problems, including malabsorption, a condition in which the gut fails to absorb nutrients and calories from food, persistent and often forceful vomiting, frequent diarrhea, foul-smelling and fatty stools (steatorrhea), and failure to grow.
Lysosomal acid lipase deficiencies occur when a person has defects (mutations) in both copies of the LIPA gene. Each parent of a person with LAL-D carries one copy of the defective LIPA gene. With every pregnancy, parents with a son or daughter affected by LAL deficiency have a one in four (25%) chance of having another affected child. A person born with defects in both LIPA genes is not able to produce adequate amounts of the LAL enzyme.
Recent media