Lysosomal Acid Lipase Deficiency

Lysosomal acid lipase deficiency is a subset of lysosomal acid lipase deficiency (LALD). There are two types of this disease, infantile LALD and late-onset LALD.

• Infantile LALD presents early in infancy and is less common and more severe than late-onset LALD.
• Late-onset LALD generally presents in mid-childhood.

Both conditions are characterized by a deficiency in a specific enzyme, which results in problems with lipid metabolism, or the body’s ability to properly break down and utilize certain fats. When these fats are not broken down and utilized, they accumulate in many of the body’s cells, tissues, and organs — eventually leading to signs of disease. LALD is one of about 50 diseases classified as lysosomal storage disorders (LSD).

Lysosomes contain specific proteins (enzymes) that are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes or do not have one of these enzymes in sufficient quantities to break down molecules for proper cell function.

Children with infantile-onset LALD generally begin exhibiting signs of the disease shortly after birth as fat molecules begin to accumulate throughout the body.

Symptoms may include:

• Enlargement of the liver and spleen (hepatosplenomegaly)
• Yellowing of the skin and whites of the eyes (jaundice)
• Developmental delay
• Poor feeding
• Fatty stools (steatorrhea)
• Vomiting
• Diarrhea
• Poor weight and height gain (failure to thrive)
• Low iron (anemia)

Children with late-onset LALD show great variation in their symptoms and the age at which signs of the disease begin to show. While many have their first symptoms in mid-childhood, some first develop symptoms in adolescence or even adulthood.

Symptoms and complications may include:

• Enlargement of the liver and spleen (hepatosplenomegaly)
• Fatty stools (steatorrhea)
• Vomiting
• Diarrhea
• High cholesterol (hypercholesteremia)
• Liver disease
• Fatty deposits in the arteries (atherosclerosis)

LALD is caused by mutations in the LIPA gene, which contains instructions for the production of an enzyme known as lysosomal acid lipase. This enzyme normally functions in the lysosomes of cells to break down various types of fats. Mutations in the LIPA gene result in a deficiency of this critical enzyme, resulting in an accumulation of fat molecules in the body, which eventually leads to dysfunction.

This genetic condition is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the LIPA gene from each of their parents.

The severity of LALD depends on the degree of deficiency of lysosomal acid lipase in the body’s cells. Children with infantile-onset LALD often have no lysosomal acid lipase and thus have a severe form of the disease. Children with late-onset LALD often have low levels of lysosomal acid lipase, which allows for the breakdown of some fat molecules, but not to the degree necessary for proper cellular function. Because of this, the disease is typically less severe.

Current approaches to both types of LALD are tailored to specific patients and may include enzyme replacement therapy (ERT) and targeted symptom management. Treatment plans require interdisciplinary collaboration and depend greatly on a patient’s specific disease presentation and a variety of additional factors.

At the Boston Children’s Lysosomal Storage Disorder (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with LALD.