Hepatic Veno-Occlusive Disease with Immunodeficiency (VODI) is a rare inherited condition that affects both the liver and the immune system. Although uncommon, it is an important diagnosis to consider in children who develop unexplained liver disease alongside recurrent infections. Understanding the genetic basis of this condition can help families access appropriate care, surveillance, and genetic counselling.
What is Hepatic Veno-Occlusive Disease?
Hepatic veno-occlusive disease (also called sinusoidal obstruction syndrome) occurs when the small veins in the liver become blocked. These tiny blood vessels, known as hepatic venules, normally allow blood to flow through the liver. When they become obstructed, blood flow is impaired, leading to liver enlargement, fluid accumulation in the abdomen (ascites), jaundice, and potentially life-threatening liver failure.
While veno-occlusive disease can sometimes occur as a complication of chemotherapy or bone marrow transplantation, VODI refers to a genetic form of the condition that presents early in life.
The Genetic Cause
VODI is caused by pathogenic variants in the SP110 gene. This gene plays an important role in regulating immune system function, particularly within white blood cells that help defend the body against infection.
When both copies of the SP110 gene carry disease-causing variants, immune cells do not function normally. This leads to combined immunodeficiency, meaning affected individuals are more vulnerable to severe or recurrent infections.
Because the same gene also appears to influence inflammatory responses in the liver, the disorder affects both immunity and liver function.
Inheritance Pattern
VODI follows an autosomal recessive inheritance pattern. This means:
- A child must inherit two non-working copies of the gene (one from each parent) to develop the condition.
- Parents who carry one altered copy are typically healthy and are called carriers.
- When both parents are carriers, each pregnancy has:
- a 25% chance of an affected child
- a 50% chance of a carrier child
- a 25% chance of a child with two working copies of the gene.
Genetic testing can confirm the diagnosis and identify carriers within the family.
Signs and Symptoms
Symptoms usually begin in infancy or early childhood. The severity can vary, but common features include:
- Hepatomegaly (enlarged liver)
- Ascites (fluid accumulation in the abdomen)
- Jaundice
- Poor growth or failure to thrive
- Recurrent or severe infections
- Fever and inflammation
In many children, the liver disease may be triggered or worsened by infections.
Because the symptoms overlap with other liver or immune conditions, diagnosis can sometimes be delayed without genetic testing.
Diagnosis
Diagnosis often involves a combination of clinical findings, laboratory tests, and genetic analysis.
Doctors may suspect VODI when a child presents with unexplained hepatic veno-occlusive disease together with immunodeficiency. Investigations may include:
- Liver imaging and blood tests
- Assessment of immune system function
- Genetic testing of the SP110 gene
Confirming a genetic diagnosis is important because it helps guide management and allows accurate counselling for the family.
Management and Treatment
Treatment focuses on managing both the liver complications and the immune deficiency.
Supportive care may include treatment of infections, immunoglobulin replacement therapy, and careful monitoring of liver function. In some cases, haematopoietic stem cell transplantation (HSCT) may be considered to address the underlying immune defect.
Early diagnosis can be critical, as timely intervention may improve outcomes and reduce complications.
The Role of Genetic Counselling
Because VODI is inherited, genetic counselling can help families understand the condition, the recurrence risk for future pregnancies, and options for testing other relatives.
At Rosalind Genetics, our clinical genetics team provides expert guidance on rare inherited conditions like VODI. Genetic testing and counselling can help families move from uncertainty to clarity, enabling informed healthcare decisions and better long-term management.
As genomic medicine continues to evolve, identifying rare conditions such as Hepatic Veno-Occlusive Disease with Immunodeficiency highlights the growing role of genetics in diagnosing complex medical disorders.
