ORPHA: 79124; DO: 0112254;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q37.1 | Hepatic venoocclusive disease with immunodeficiency | 235550 | Autosomal recessive | 3 | SP110 | 604457 |
A number sign (#) is used with this entry because of evidence that hepatic venoocclusive disease with immunodeficiency (VODI) is caused by homozygous mutation in the SP110 gene (604457) on chromosome 2q37.
Hepatic venoocclusive disease with immunodeficiency syndrome (VODI) is an autosomal recessive primary immunodeficiency associated with hepatic vascular occlusion and fibrosis. The immunodeficiency is characterized by severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, and absent tissue plasma cells (summary by Roscioli et al., 2006).
In Australia, Mellis and Bale (1976) described 5 infants in 3 families who died between ages 2 and 7 months with venoocclusive disease of the liver. In 2 of the families the parents were cousins. No exogenous explanation such as pyrrolizidine alkaloid, which is known to cause hepatic venoocclusive disease and at times affects multiple family members (Selzer and Parker, 1951), could be identified. All 5 infants had evidence suggesting immunodeficiency, such as hypogammaglobulinemia, multiple infections and lymphoid tissue deficient in germinal centers and mature plasma cells. Microcephaly, multiple small cerebral softenings, and left atrial endocardial fibrosis were also found at autopsy.
Roscioli et al. (2006) identified 6 children from 5 families of Lebanese ethnicity who presented between 3 and 7 months of age with either a combined T and B cell immunodeficiency and/or a personal or family history of hepatic venoocclusive disease. Clinical correlates of immunodeficiency included Pneumocystis jerovici infection, enteroviral infection, or mucocutaneous candidiasis, but there was no evidence of mycobacterial infection. Hepatic venoocclusive disease was verified by biopsy in at least 1 individual in each sibship and was indistinguishable clinically and pathologically from the sinusoidal obstruction syndrome described after hematopoietic stem cell transplantation. Absent lymph node germinal centers and absent tissue plasma cells were other features. The lack of recognized association of immunodeficiency with hepatic venoocclusive disease in other classes of immunodeficiency suggested that the hepatic venoocclusive disease is not a secondary event but a primary feature of VODI.
The transmission pattern of VODI in the families reported by Roscioli et al. (2006) was consistent with autosomal recessive inheritance.
VODI has an estimated frequency of 1:2,500 live births in the Lebanese population of Sydney, Australia, with 19 cases identified over a period of 30 years (Roscioli et al., 2006).
VODI is associated with an 85% mortality if unrecognized and untreated with intravenous immunoglobulin and Pneumocystis jerovici prophylaxis (Roscioli et al., 2006).
In affected members of 4 families with VODI, Roscioli et al. (2006) identified a homozygous single-base deletion, 642delC (604457.0001), in the SP110 gene. In an affected member of another family with VODI, they identified a homozygous single-base deletion, 40delC (604457.0002), in the SP110 gene on a different haplotype background from that in the other 4 families.
Mellis, C., Bale, P. M. Familial hepatic veno-occlusive disease with probable immune deficiency. J. Pediat. 88: 236-242, 1976. [PubMed: 1249685] [Full Text: https://doi.org/10.1016/s0022-3476(76)80988-2]
Roscioli, T., Cliffe, S. T., Bloch, D. B., Bell, C. G., Mullan, G., Taylor, P. J., Sarris, M., Wang, J., Donald, J. A., Kirk, E. P., Ziegler, J. B., Salzer, U., McDonald, G. B., Wong, M., Lindemann, R., Buckley, M. F. Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease. Nature Genet. 38: 620-622, 2006. [PubMed: 16648851] [Full Text: https://doi.org/10.1038/ng1780]
Selzer, G., Parker, R. G. F. Senecio poisoning exhibiting as Chiari's syndrome: a report on twelve cases. Am. J. Path. 27: 885-907, 1951. [PubMed: 14868767]