Hepatic veno-occlusive disease with immunodeficiency (VODI) is characterized by (1) primary immunodeficiency and (2) terminal hepatic lobular vascular occlusion and hepatic fibrosis manifest as hepatomegaly and/or hepatic failure. Onset is before age 12 months. The immunodeficiency comprises severe hypogammaglobulinemia, clinical evidence of T-cell immunodeficiency with normal numbers of circulating T cells, absent lymph node germinal centers, and absent tissue plasma cells. Bacterial and opportunistic infections including Pneumocystis jerovici infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections occur. VODI is associated with 90% mortality overall and 100% mortality if unrecognized and untreated with intravenous immunoglobulin (IVIG) and Pneumocystis jerovici prophylaxis.
Diagnosis is based on low serum concentrations of IgA, IgM, and IgG for age, normal lymphocyte numbers, normal CD4 and CD8 percentages, histologic examination of the liver (or hepatic ultrasonography and Doppler ultrasonography if hepatic biopsy is not possible), and molecular genetic testing of SP110, the only gene known to be associated with VODI.
VODI is inherited in an autosomal recessive manner. The parents of an affected child are obligate heterozygotes (carriers) and therefore carry one mutant allele. Heterozygotes are asymptomatic. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if both disease-causing mutations in a family are known.