Wolman disease

Overview

Also known as early onset Lysosomal Acid Lipase (LAL) Deficiency, Wolman disease is an inherited metabolic disease that results in the buildup of fats in the tissues and organs leading to liver problems and growth failure in babies that is usually fatal by one year of age.

Symptoms

Babies with early onset LAL Deficiency may seem healthy at birth, but as soon as 1 or 2 months of age, the baby may start to show signs of the disease and get very sick very quickly. The baby is at high risk of dying before the first birthday.

The signs and symptoms can include although all may not be experienced:

  • Feeding difficulties with frequent vomiting
  • Diarrhea (loose frequent or fatty stools)
  • Swelling of the belly (abdominal distention)
  • Enlargement of the liver and spleen (hepatosplenomegaly)
  • Failure to gain weight or sometimes even weight loss
  • Hardening of the glands above the kidneys (adrenal glands)

Causes

LAL Deficiency is a genetic condition, which means is it caused by our genes. Sometimes our genes do not work properly because there are changes in their codes, known as mutations. LAL Deficiency is caused by mutations in the LIPA gene. This gene tells our body how to make the LAL enzyme. The LAL enzyme breaks down fatty material into forms that our body can use. A person with LAL Deficiency is missing the enzyme needed to break down fats.

LAL Deficiency is also an inherited condition. It is an autosomal recessive disease, which means a person with the disease inherits two mutations or non-working copies of the LIPA gene.

Diagnosis

Before birth (prenatally) testing is possible: during the first trimester by a procedure known as chorionic villus sampling (CVS) and by a different procedure called amniocentesis during the second trimester.

A diagnosis in a baby may be suspected based on family history or the identification of certain symptoms such as enlarged liver or stomach and intestine problems. The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history (including family history) and special tests that reveal absence or deficient activity of the LAL enzyme in certain cells and tissues of the body. Confirming that there are mutations (genetic variations) in both copies of the LIPA gene is also considered a positive diagnosis.

Testing information is available at the following websites:

https://www.bcm.edu/geneticlabs/test_detail.cfm?testcode=4504&show=1

http://www.jefferson.edu/lysolab/tests.cfm

http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2395

 

A laboratory in Scotland is offering a simpler test that provides quicker results. Your physician may also contact Yorkhill Laboratory in Scotland via email [email protected]

Treatment

Currently, there are no treatments that have been approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for LAL Deficiency. Care is mainly focused on reducing specific complications, and these complications may differ between patients. Specific interventions may include:

  • A change from breast or normal bottle formula to a specialized low fat formula
  • Introduction of feeding through a vein (intravenous)
  • Antibiotics for infections
  • Steroid replacement therapy because of concerns about hormonal function
  • Genetic counseling may be helpful for families impacted by this disease.

Investigational Therapies

Enzyme replacement therapy

Researchers are currently studying enzyme replacement therapy for LAL Deficiency.

Enzyme replacement therapy (ERT) involves replacing a missing enzyme in individuals who are deficient or lack the particular enzyme in question.

SBC-102 is being investigated as a potential treatment for LAL Deficiency, including the early onset form. For information about the clinical trial, please visit http://www.clinicaltrials.gov/ct2/resultx?term=synageva

Hematopoietic stem cell transplantation:

Some infants with the early onset form of LAL Deficiency have had an experimental therapy called hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplant. Hematopoietic stem cells are specialized cells found in the bone marrow (the soft spongy material found in long bones). HSCT for infants with LAL Deficiency has been associated with a high risk of serious complications including death, graft-versus-host disease and other long-term and late effects. More research is necessary to determine the long-term safety and effectiveness of this potential therapy.

Resources

LAL Solace is a support organization that was created to bring LAL Deficiency patients and families together to share experiences, knowledge, and compassion. Please visit www.LALsolace.org to learn more.