SNP Shot: Genomic Insights

Lysosomal acid lipase deficiency (LAL-D) is a genetic disorder that disrupts how the body processes fats and cholesterol (lipid metabolism). People with LAL-D accumulate harmful levels of fats (lipids) in cells and tissues, leading primarily to liver problems. There are two main forms of LAL-D: a severe form that appears in infancy, and a less severe form that can manifest from childhood into adulthood.

The severe, early-onset form of LAL-D causes rapid lipid buildup, especially in the liver, soon after birth. This lipid accumulation results in an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, jaundice (yellowing of the skin and eyes), vomiting, diarrhea, fatty stools (steatorrhea), and difficulty absorbing nutrients from food (malabsorption). Affected infants often have calcium deposits on the adrenal glands (small glands near the kidneys), low iron levels in the blood (anemia), and developmental delays. Liver damage progresses quickly, leading to cirrhosis. Infants with this severe form experience multi-organ failure and severe malnutrition, and typically do not survive beyond their first year.

The later-onset form of LAL-D presents with a wider range of symptoms that usually begin in mid-childhood, but can appear at any point up to late adulthood. Nearly all affected individuals experience an enlarged liver (hepatomegaly), and an enlarged spleen (splenomegaly) is also common. Approximately two-thirds develop liver fibrosis, which can progress to cirrhosis. Around one-third of individuals with the later-onset form experience malabsorption, diarrhea, vomiting, and steatorrhea. Blood tests in individuals with this form of LAL-D may reveal increased liver enzymes and high cholesterol levels.

Some individuals with the later-onset form of LAL-D develop atherosclerosis, a buildup of fatty deposits on artery walls. While atherosclerosis is common in the general population, it tends to occur at a younger age in people with LAL-D. This narrowing of the arteries increases the risk of heart attack or stroke. The lifespan of individuals with later-onset LAL-D varies depending on the severity of their associated health issues.

The two forms of LAL-D were previously considered separate diseases. The early-onset form was called Wolman disease, and the later-onset form was called cholesteryl ester storage disease. Although they share the same genetic cause and are now classified as variations of a single condition, these former names are still sometimes used to distinguish between the different presentations of LAL-D.

Inheritance:

LAL-D follows an autosomal recessive inheritance pattern. This means that an individual must inherit two mutated copies of the responsible gene, one from each parent, to develop the condition. Parents who each carry one copy of the mutated gene are called carriers and usually do not exhibit any symptoms of LAL-D.