c.380A>G
Case#: N/A. Patient was the only one included in this paper. Male. Age of Onset: 9 y.o. Age of evaluation: 42 y.o onwards. Age of Death: ~49 y.o. Origin in Portugal, ethnicity not specified.
DiseaseAssertion: Evans Syndrome
FamilyInfo: No familial segregation analysis could be performed as the patient′s first‐degree relatives (reportedly healthy) refused genetic testing, and the patient had no progeny. Additionally, when the patient was diagnosed and treated for other health conditions, it was noted that "There was no relevant family history".
CasePresentingHPOs: ORPHA:1959 (Evan's syndrome), HP:0002014 (Diarrhea), HP:4000055 (Intestinal Inflammation), HP:0002719 (Severe/Recurrent Infections), HP:0000403 (Recurrent Otitis), HP:0002254 (Intermittent Diarrhea), HP:0001873 (Severe Thrombocytopenia), HP:0002090 (Pneumonia), HP:0004315 (low IgG), HP:0002720 (low IgA), HP:0001082 (Cholecystitis), HP:0001433 (Hepatosplenomegaly), HP:0008711 (Benign prostatic hypertrophy), HP:0012227 (urethral stricture), HP:0003508 (Proportionate Short Stature), HP:0001888 (Lymphopenia), HP:0410385 (Low levels of CD8+ T cells), HP:0410378 (Low levels of CD4+ T cells),
CaseHPOFreeText: Lymphoproliferation, mild ileal inflammatory infiltrate on histology and hemolysis, lower limb cellulitis, IgE and IgD levels were undetectable, but IgM levels were normal, Bilateral osteonecrosis of femoral head and condyles at age 43, Facial vitiligo, Hemoglobin 12.5 g/L; leukocytes: 8700/μL; platelets 28000/μL, trabeculated bladder.
Duodenal, ileal and bladder biopsy: inflammatory infiltrate (not characterized) Negative: direct Coombs, ANA, EBV DNA, CMV DNA, hepatitis B, C, HIV, proteinuria, urinary Ig loss Antiplatelet Ab positive.
Normal total leukocyte count but patient had lymphopenia.
Antidiphtheria Ab: 0.44 UI/mL (protection titer >1.0 UI/mL); peripheral blood mononuclear cell proliferation to PHA, PPD, and Candida were slightly reduced.
Normal levels of CD3+ and CD4+ but low levels of CD8+ (T cells), Low levels of B cells, NK cells and CD4+ (CD45RA+ and CD45RO+) cells. Normal levels of CD45RA+ but high levels of CD45RO+ (CD8 + T cells).
Born to nonconsanguineous parents.
CaseNotHPOs: N/A
CaseNotHPOFreeText: In 2013, the 45‐year‐old patient was admitted for sepsis. An elective total right hip replacement 6 months before had been followed by recurrent urosepsis. Postoperative diagnosis: recurrent urosepsis caused by Enteroccocus faecalis, Klebsiella pneumoniae and Pseudomonas aeruginosa.
For the next 3 years, the patient remained free of infection on IVIG replacement (0.6–0.8 g/kg) every 3–4 weeks, with a median IgG concentration of approximately 6 g/L. In October 2016, he underwent a transurethral resection of the prostate and soon afterward developed diarrhea and significant weight loss. He was again admitted to our hospital, but after extensive investigation, no infectious or immune‐mediated cause could be found. There was an excellent response to a short course of a higher dose of oral prednisolone (30 mg/day, tapered over the next 2 months to 5 mg/day). In February 2017, he was admitted to his local hospital with left‐sided epididymo‐orchitis and rapidly died from hospital‐acquired pneumonia.
CasePreviousTesting: Broad genetic screening using a custom panel of many immune‐related genes using an ion proton next‐generation sequencer, followed by Sanger sequencing, was performed at the Laboratory of Clinical and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. See Table 1.
GenotypingMethod: CTLA‐4 sequencing was performed after amplification of the four exons. See Table 1.
PreviouslyPublished: N/A
Variant: NM_005214.5:c.380A>G
ClinVarID: 949358
CAID: CA350138668
gnomAD: Not found
SupplementalData: N/A
Note: Not functionally tested using transendocytosis