Clinical Guidance

No significant difference in the clinical manifestations of VODI is observed between individuals with different pathogenic variants. The majority of SP110 pathogenic variants are small deletions or duplications leading to a frame shift with consequent protein truncation. Milder phenotypes may be seen in individuals with SP110 missense variants; however, reports of affected family members dying in infancy with typical VODI presentations precludes genotype-phenotype correlation .

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"

Diagnostic Criteria

Clinical diagnostic criteria for hepatic veno-occlusive disease with immunodeficiency (VODI) have been established .

Suggestive Findings

VODI should be suspected in individuals with the following clinical, laboratory, imaging, and histopathologic findings and family history.

Clinical findings

• Clinical evidence of immunodeficiency with bacterial and opportunistic infections including Pneumocystis jirovecii infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections

• Hepatomegaly or evidence of hepatic failure, not explained by other factors, in the affected individual or a first-degree relative

Note: Hepatic veno-occlusive disease (hVOD; also known as sinusoidal obstruction syndrome) is usually present and pathognomonic but may not be found, or may have resolved.

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"

Differential Diagnosis

Hepatic veno-occlusive disease (hVOD). The primary differential diagnosis for hVOD alone is environmental alkaloid or sinusoidal cell toxicity. Hepatic veno-occlusive disease has also been reported in association with alcoholic cirrhosis , ataxia-telangiectasia , osteopetrosis (see CLCN7-Related Osteopetrosis), and hypereosinophilic syndrome (OMIM 607685). Immunodeficiency. Other combined immunodeficiency disorders and HIV should be considered in the differential diagnosis for the immune phenotype. To date, there has been no report of SP110 pathogenic variants in individuals described to have hVOD without immunodeficiency.

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"

Management Guidelines

No clinical practice guidelines for hepatic veno-occlusive disease with immunodeficiency (VODI) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with VODI, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Hepatic Veno-Occlusive Disease with Immunodeficiency: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Immune function

| • Eval by immunologist

• Serum Ig levels

• T B cell numbers percentages

• T cell proliferative response to mitogens

| More extensive immune testing for number of memory B T cells intracellular cytokine (IL-2, IL-4, IL-6, IFN-) responses to stimulation SP110 expression (flow cytometry), if available

Liver function

| • Serum aminotransferases, bilirubin, albumin

• Complete blood count to assess anemia thrombocytopenia

|

Clotting profile hepatic Doppler ultrasound exam prior to liver biopsy for hVOD | Evidence of impaired clotting /or significant portal hypertension contraindicates hepatic biopsy.

Neurologic

| Consider baseline CNS imaging. | Head ultrasound if anterior fontanelle is open

Growth/Nutrition

| • Early involvement of dietary support to optimize nutritional intake

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"

Clinical Guidance

Agents known to predispose to hepatic veno-occlusive disease (e.g., cyclophosphamide and Senecio alkaloids/ bush teas) should be avoided.

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. Hepatic Veno-Occlusive Disease with Immunodeficiency: Recommended Surveillance

Source: GeneReviews — "Hepatic Veno-Occlusive Disease with Immunodeficiency"