hepatic veno-occlusive disease-immunodeficiency syndrome

Hepatic veno-occlusive disease-immunodeficiency syndrome is a very rare condition that affects both the liver and the immune system. It is characterized by a marked deficiency of immunoglobulins, impaired T and B cell function, absent lymph node germinal centers, and the development of veno-occlusive disease in the liver. The genetic basis involves pathogenic variants in the SP110 gene. This condition is inherited in an autosomal recessive pattern, which means an affected individual must inherit two altered copies of the gene. Its rarity is underscored by the fact that it affects fewer than 1 in 1,000,000 people.

The clinical presentation of this syndrome reflects its dual impact on both the immune system and the liver. Affected individuals typically exhibit severe hypogammaglobulinemia and a combined T and B cell immunodeficiency, which predisposes them to recurrent infections. In addition, the absence of lymph node germinal centers and tissue plasma cells can be noted alongside the development of hepatic veno-occlusive disease. Not all individuals experience all findings, and severity varies considerably between cases.

Hepatic veno-occlusive disease-immunodeficiency syndrome is caused by pathogenic variants in the SP110 gene. The SP110 protein plays an important role in the regulation of immune responses, and disruptions in its function lead to the combined immunodeficiency and associated liver pathology seen in this condition. This syndrome is inherited in an autosomal recessive pattern, meaning that both copies of the gene must be affected for the condition to manifest. It is more common when parents share a common ancestor, as this increases the likelihood that both carry the same rare genetic variant.

Currently, management of hepatic veno-occlusive disease-immunodeficiency syndrome focuses on supportive care and symptomatic treatment since no FDA-approved therapies exist for this condition. Treatment is highly individualized and typically involves a multidisciplinary team to address both immune deficiencies and liver complications. Patients are managed by optimizing immune function and monitoring liver health, and regular consultations with their healthcare team help determine the most appropriate interventions. Genetic counseling is also recommended to provide guidance on inheritance and family planning.

Outcomes for individuals with hepatic veno-occlusive disease-immunodeficiency syndrome vary depending on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals experience a stabilization of symptoms, although the course of the condition can differ significantly from one person to another. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists in immunology to discuss potential management options and to help navigate ongoing care.