Wolman disease (infantile-onset LAL deficiency)

Wolman disease is a lysosomal storage disorder. Lysosomes are the parts of a cell that break down and recycle used material. One of their enzymes, lysosomal acid lipase, breaks down two kinds of fat: cholesteryl esters and triglycerides. In Wolman disease, this enzyme is missing or almost completely missing.

Doctors now often call it the infantile-onset form of lysosomal acid lipase deficiency (LAL-D). A later-onset form, once called cholesteryl ester storage disease, has the same cause but some working enzyme. It can start anywhere from childhood to late adulthood. This page is about the infantile form, which experts describe as a medical emergency.

Wolman disease is caused by changes in both copies of the LIPA gene. This gene carries the instructions for making lysosomal acid lipase.

It is inherited in an autosomal recessive pattern. Each parent usually carries one changed copy and has no symptoms. When both parents are carriers, each pregnancy has a 1 in 4 chance of a child with the condition.

It is not caused by anything a parent did, and it cannot be caught from another person. A genetic counselor can explain what test results mean for brothers, sisters and future pregnancies.

Signs usually start in the first weeks of life. Babies have vomiting, diarrhea and fatty stools. They cannot absorb enough nutrition from food, so they gain weight poorly. The liver and spleen become very large (hepatosplenomegaly), and the skin and eyes may turn yellow (jaundice).

Many babies have calcium deposits in the adrenal glands, the small glands on top of the kidneys. Low red blood cells (anemia) are common, and scar tissue builds up quickly in the liver.

Many babies also have strong inflammation throughout the body. In some, the immune system overreacts in a dangerous way called hemophagocytic lymphohistiocytosis (HLH). A 2024 expert review says HLH is common at diagnosis.

Without disease-specific treatment, the illness moves very fast. In an international study of 35 babies diagnosed between 1985 and 2012 who did not have enzyme therapy, half had died by 3.7 months of age.

Wolman disease is suspected in a baby with vomiting, diarrhea, poor weight gain and a very large liver and spleen in the first weeks of life. Calcium deposits in the adrenal glands, seen on an x-ray, ultrasound or CT scan, strongly suggest it, but their absence does not rule it out. Some babies first come to attention with HLH.

The key test measures lysosomal acid lipase activity. A 2024 expert review says a dried blood spot test is the quickest and most reliable way to do this, and that it should be done right away when the disease is suspected. In Wolman disease, activity is absent or below 1 percent of normal. Finding changes in both copies of the LIPA gene also confirms it.

Newborn screening for this condition was not available when that review was written. After one UK baby treated right after birth did well, the doctors raised the question of adding Wolman disease to newborn screening.

Care teams treat Wolman disease as an emergency. A 2024 expert review says the enzyme should be measured right away when the disease is suspected, and that enzyme therapy should start as soon as possible, ideally before 2 to 3 months of age.

Sebelipase alfa (Kanuma) is a lab-made copy of the missing enzyme, given into a vein. The European Union and the United States both approved it in 2015. For babies with the fast-moving form, the U.S. label starts with a weekly infusion and raises the dose if the baby does not respond well enough. Some expert centers now start at higher doses. The medicine carries a boxed warning for severe allergic reactions, including anaphylaxis. In England, NICE recommended it in 2024 for Wolman disease when treatment starts at age 2 or under.

A low-fat diet is the other half of treatment. Many babies are first fed by vein, then with special low-fat formula, often through a feeding tube. In two clinical trials of 19 babies, an estimated 79% were alive at 12 months of age and 68% at 5 years.

Enzyme therapy has limits. It is lifelong and costly, and it needs a reliable line into a vein. Some children make antibodies against the medicine that weaken it. In one UK center, most children on enzyme therapy alone still needed a strict low-fat diet because of ongoing gut problems.

A donor stem cell transplant is the other main option. The donor’s cells grow into healthy white blood cells, including the cells where fat builds up, and they make the missing enzyme. Before enzyme therapy, transplant results were poor because babies were so sick. Now some centers give enzyme therapy and a low-fat diet first, to make the baby stronger, and then transplant. European guidelines from 2025 and 2026 call transplant for Wolman disease a clinical option, decided case by case by an expert team.

The first months are often spent in the hospital. Babies may need nutrition by vein, blood transfusions and treatment for inflammation, along with their infusions. A 2024 expert review notes that even with early treatment, the first months to one year of life can be hard.

Feeding is a big part of daily life. A specialist dietitian plans a carefully limited low-fat diet, and many children are fed by tube for a time. In one UK center’s report, three of the four children who survived a transplant were slowly able to move to a normal diet. After transplant, their diarrhea took up to about 10 months to settle.

Families weigh lifelong infusions and diet limits against the risks of a transplant, such as serious infections and graft-versus-host disease, when donor immune cells attack the body. England’s NICE noted that people may choose a transplant to reduce the need for the restricted diet and regular infusions, but that a transplant carries risks. Patient experts told NICE that most families preferred to stay on enzyme therapy and saw a transplant as a backup if the medicine stopped working.

When a transplant is used for Wolman disease, the cells come from another person. The donor’s healthy cells replace the child’s blood-forming system and supply the missing enzyme.

In a UK report of five children who had enzyme therapy and then a transplant, the donors were a matched brother or sister, another matched relative, a half-matched relative, an unrelated adult volunteer and unrelated cord blood. Four of the five were alive when the report was written.

For lysosomal storage disorders like this one, 2026 European guidelines prefer a well-matched unrelated donor who does not carry the gene change over a family donor who carries one changed copy. Parents are carriers, and brothers and sisters may be too, so a registry donor or a cord blood unit can matter.

Because so few babies have Wolman disease, a shortage of registry donors is not the main barrier. Fast diagnosis and early treatment are the biggest needs. Joining a registry still helps the many other patients who need an unrelated donor.

Before enzyme therapy, almost no babies with Wolman disease lived past their first year. Enzyme replacement started early has changed the outlook, and many treated children are now growing up. Published reports follow treated children for up to about 10 years, so how they will do as adults is not yet known.

A baby’s outlook depends on how sick they are when treatment starts, whether HLH or antibodies against the medicine develop, and how well the gut recovers. Transplant results have improved when enzyme therapy is given first, but they come from small groups of children.