Table 3.

Clinical Features of Individuals Homozygous for SP110 Pathogenic Variants

Affected IndividualSP110 (LRG_109) Pathogenic VariantPresentationSerum IgsMemory T/B CellsT Cell CytokinesClinical FindingsDeceased
A II.1 1
Lebanese		c.642delC in exon 5Age 5 mos: immunodeficiency, thrombocytopenia, SOS↓N/AN/ALeft hemiparesis 2, recurrent hVOD w/GVHD post-HSCTYes
B II.1 1
Lebanese		Age 7 mos: immunodeficiency↓N/AN/AChronic lung disease secondary to recurrent aspirationYes (age 19 yrs)
B II.2 1
Lebanese		Age 6 mos: hepatosplenomegaly, ascites, SOS↓↓↓Well until 18 yrs (developed paraparesis, urinary retention, cerebral lesions)No
C II.1 1
Lebanese		Age 4 mos: hepatosplenomegaly, ascites, SOS, thrombocytopenia, mucocutaneous candidiasis↓↓↓Chronic liver disease, portal hypertension post-hepatic transplantationYes
D II.1 1
Lebanese		Age 3 mos: hepatosplenomegaly, ascites, SOS↓ 3↓↓Hemophagocytic syndrome post-hepatic transplantationYes
16 4
Lebanese		c.642delC in exon 5Age 3 mos: hepatosplenomegaly, ascites, SOS↓↓↓Pulmonary hemorrhage, multiorgan failureYes
5 4
Lebanese		c.642delC in exon 5Age 3 mos, respiratory distress↓↓N/ASIADH, idiopathic cerebrospinal leukodystrophyNo
6 4
Lebanese		c.642delC in exon 5Age 3 mos: chronic cough, diarrhea
Age 8 yrs: hepatosplenomegaly
Age ≥12 yrs: hVOD		↓N/AN/AIdiopathic left frontal lobe calcified cyst, epilepsy, CMV colitis, post-diarrheal encephalomyelitis w/lower limb paralysis, cerebrospinal leukodystrophy, esophageal candidiasis, duodenal lymphocytic infiltrateNo
7 4
Lebanese		c.642delC presumed 5Age 2 mos: chronic diarrhea, failure to thrive, middle ear & respiratory infections, hepatosplenomegaly, thrombocytopeniaN/AN/AN/AMicrocephaly, hepatic biopsy consistent w/SOSYes, 11 mos from diarrhea leading to septic shock
8 4
Lebanese		c.642delC presumed 5Age 5 mos: upper respiratory illness
Age 8 mos: chronic diarrhea, hepatomegaly, thrombocytopenia		N/AN/AN/AHepatic biopsy consistent w/SOSYes, 3.5 yrs from diarrhea leading to septic shock
9 4
Lebanese		c.642delC presumed 5Age 2 mos: ascites, hepatomegaly, anemia, thrombocytopeniaN/AN/AN/AHepatic biopsy consistent w/SOSYes, 2.5 mos from otitis, diarrhea, pneumonia
E I.1 1
Lebanese		c.40delC in exon 2Age 3 mos: immunodeficiency, thrombocytopenia, hepatosplenomegaly w/out definite evidence of SOS↓N/AN/AEnteroviral & P. jirovecii infectionYes
4 4
Hispanic		c.78_79delinsAT (p.Ile27Leu) in exon 2Age 5 mos: hepatosplenomegaly, fever, respiratory distress, pancytopenia↓↓↓Stable & wellNo
1 4
Italian		c.319_325dup GGTGCTT in exon 4Age 11 mos: hepatosplenomegaly, disseminated CMV, rotavirus gastroenteritis, vulvar abscesses, SOS↓ initially↓N/ARecovering from hVOD, wellNo
2 4
Italian		c.667+1dup exon 5 splice siteAge 3 mos: hepatosplenomegaly, failure to thrive, respiratory distress/lung fibrosis, diarrhea↓↓N/AHepatic biopsy consistent w/sinusoidal dilatation, moderate central vein & perivenular subsinusoidal fibrosis; stable w/improvementNo
3 4
Palestinian Arab		c.373del in exon 4Age 3 mos: diagnosis of VODI confirmed w/cascade testing prior to illness onset. No hepatomegaly or liver function abnormalitiesN/AN/AN/AStable & wellNo

Modified from Roscioli et al [2006]

CMV = cytomegalovirus; GVHD = graft-versus-host disease; HSCT = hematopoietic stem cell transplantation; hVOD = hepatic veno-occlusive disease; SIADH = syndrome of inappropriate antidiuretic hormone secretion; SOS = sinusoidal obstruction syndrome

Note: Although families A, B, and C are not known to be related, they are believed to have a common ancestor. Individuals included in the initial homozygosity mapping analysis: A II.1, B II.1, B II.2, C II.1, 16 (‘G’ in initial analysis), and 5 (‘J’ in initial analysis).

Affected individual designations are those used in the articles cited.

1.
2.

Secondary to cerebral white matter abnormality

3.

IgA and IgM serum concentrations increased to lower limit of normal while on IVIG.

4.
5.

The pathogenic variant listed is a known familial variant. While sequence analysis was not performed on this affected individual, c.642delC is presumed to be the pathogenic variant based on the family history.

From: Hepatic Veno-Occlusive Disease with Immunodeficiency

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