Hepatic veno-occlusive disease with immunodeficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hepatic veno-occlusive disease with immunodeficiency (VODI) is a disorder of the liver and immune system. Its signs and symptoms typically appear before six months of age.

Hepatic veno-occlusive disease is a condition that blocks (occludes) small veins in the liver, disrupting blood flow in this organ. This condition can lead to enlargement of the liver (hepatomegaly), a buildup of scar tissue (hepatic fibrosis), and liver failure.

Children with VODI have immune systems that do not function normally. They are vulnerable to recurrent infections that are caused by certain bacteria, viruses, and fungi. Affected individuals experience frequent colds or bouts of pneumonia. The infections are likely related to lower-than-normal levels of immune system cells, including special proteins called antibodies or immunoglobulins, particularly immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA). Antibodies attach to specific foreign particles, marking them for destruction. These infections are usually serious and may be life-threatening. In most people with VODI, infections occur before hepatic veno-occlusive disease becomes evident.

Some children with VODI have neurological problems due to blocked blood flow in the brain.

If untreated, children with VODI do not survive past infancy. With treatment, many people with VODI can live into childhood and sometimes into their teens.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

VODI is caused by variants (also called mutations) in the SP110 gene. This gene provides instructions for making a protein called SP110 nuclear body protein. This protein plays a role in cell division, the self-destruction of cells that are damaged or no longer needed (apoptosis), and the normal function of the immune system. This protein likely helps regulate the activity of genes that are needed for the body's immune response to foreign invaders, such as viruses and bacteria.

Variants in the SP110 gene prevent cells from making enough functional SP110 nuclear body protein to allow the immune system to fight off infections effectively. This loss of protein causes immunodeficiency in people with VODI. It is unclear whether a lack of functional protein causes liver disease or if the liver problems are a result of unregulated apoptosis or recurrent infections.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

VODI appears to be a rare disorder; more than 20 affected families have been reported worldwide. Though most of the people with this condition have been of Lebanese ancestry, this disorder has also been identified in individuals from other countries.

Understanding terms used in the source

These definitions explain medical words used above. A definition is not evidence that another condition is present, and it does not predict how a symptom will develop. Ask the clinician which terms apply to the actual examination or test result.

Hepatic fibrosis

The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.

Immunodeficiency

Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.

Recurrent

Applies to a sign, symptom or manifestation that occurs multiple times separated by intervals in which the sign, symptom, or manifestation is not present.

Affected

This term applies to a family member who is diagnosed with the same condition as the individual who is the primary focus of investigation (the proband).

Which doctor should you see?

The suggested department for discussing Hepatic veno-occlusive disease with immunodeficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.