Table 1.
Patient genotype, phenotype, demographics and laboratory results.
| FAMILY A | FAMILY B | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| I-1 | I-2 | II-1 | II-2 | I-1 | I-2 | II-1 | II-2 | II-3 | II-4 | ||
| Genotype IRAK4 (HGVS cDNA) |
WT/c.C877T | WT/c.G958T | c.G958T/c.C877T | c.G958T/c.C877T | WT/c.A86C | WT/ c.161 + 1G>A |
c.A86C/c.161 + 1G>A | c.A86C/c.161 + 1G>A | c.A86C/c.161 + 1G>A | WT/WT | |
| IRAK-4 (HGVS protein) | WT/p.Q293* | WT/p.D320Y | p.Q293*/p.D320Y | p.Q293*/p.D320Y | WT/p.Q29P | WT/- | p.Q29P/- | p.Q29P/- | p.Q29P/- | WT | |
| Functional impact of variant | Deleterious: premature stop codon | Unknown | Deleterious: premature stop codon/Unknown | Deleterious: premature stop codon/Unknown | Unknown | Deleterious: abolition of splice site |
Unknown/ Deleterious: abolition of splice site |
Unknown/ Deleterious abolition of splice site |
Unknown/ Deleterious abolition of splice site |
N/A | |
| Zygosity | Heterozygous | Heterozygous | Compound heterozygous | Compound heterozygous | Heterozygous | Compound heterozygous | Compound heterozygous | Compound heterozygous | Compound heterozygous | WT | |
| Affected | No | No | Yes | Yes | No | No | Yes | Yes | Yes | No | |
| Demographics | |||||||||||
| Ethnicity | White British | Chinese | Mixed | Mixed | Syrian | White Polish | Mixed | Mixed | Mixed | Mixed | |
| Sex | M | F | M | M | M | F | F | F | F | M | |
| Age at first presentation | N/A | N/A | 23 months | 24 months | N/A | N/A | 8 weeks | 3 weeks | Neonate | N/A | |
| Clinical Features | |||||||||||
| Recurrent fevers | N/A | N/A | Yes | Yes | N/A | N/A | Yes | Yes | Yes | No | |
| Persistently elevated inflammatory markers | N/A | N/A | Yes | Yes | N/A | N/A | Yes | Yes | Yes | No | |
| Hepatomegaly | N/A | N/A | Yes | Yes | N/A | N/A | Yes | Yes | No | No | |
| Splenomegaly | N/A | N/A | Yes | Yes | N/A | N/A | Yes | Yes | Yes | No | |
| Anemia | N/A | N/A | Yes | Yes | N/A | N/A | Yes | Yes | Yes | No | |
| Transaminitis | N/A | N/A | Yes | Yes | N/A | N/A | Yes | Yes | UK | No | |
| Biochemical features | pre/post- splenectomy | ||||||||||
| Hb (g/L; RR 115-145) | NI | NI | 76 | 95 | NI | NI | 43/109 | 64 | 80 | 129 | |
| CRP (mg/L; RR 0-20) | NI | NI | 125 | 49 | NI | NI | 107/85 | 60 | 39 | <5 | |
| ESR (mm/hr; RR 0-10) | NI | NI | 135 | 116 | NI | NI | UK/127 | 343 | 100 | 6 | |
| SAA (mg/L; RR <10) | NI | NI | 101 | 196 | NI | NI | UK/97 | 58 | 202 | 3.5 | |
| ALT (U/L; RR 10-25) | NI | NI | 68 | 46 | NI | NI | <6/58 | 86 | 43 | 32 | |
| Imaging | |||||||||||
| Abdominal ultrasound | NI | NI | Hepato- splenomegaly |
Hepato- splenomegaly |
NI | NI | Hepato- splenomegaly |
Hepato- splenomegaly |
Splenomegaly | NI | |
| CT - head | NI | NI | NI | Bilateral temporal subcortical calcifications. | NI | NI | NI | Bilateral temporal cortical calcifications. | NI | NI | |
| MRI head | NI | NI | Past choroid plexus hemorrhage. No calcification. | Bilateral (left>right) temporal encephalitis with vasogenic oedema and subcortical and cortical enhancement. | NI | NI | Normal | Bilateral temporal cortical hyperintensities & enhancement. Volume reduction of right temporal lobe and hippocampus. |
Symmetrical signal abnormality in the medial temporal regions and white matter adjacent to frontal horns | NI | |
RR, Reference Range; UK, Unknown; N/A, Not applicable; NI, Not indicated; ND, Not done; Hb, hemoglobin; RBC, red blood cells; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A; ALT, alanine aminotransaminase; CT, computed tomography; MRI, magnetic resonance imaging.